Bio-inspired Materials Give Boost to Regenerative Medicine – Bioscience Technology

What if one day, we could teach our bodies to self-heal like a lizards tail, and make severe injury or disease no more threatening than a paper cut?

Or heal tissues by coaxing cells to multiply, repair or replace damaged regions in loved ones whose lives have been ravaged by stroke, Alzheimers or Parkinsons disease?

Such is the vision, promise and excitement in the burgeoning field of regenerative medicine, now a major ASU initiative to boost 21st-century medical research discoveries.

ASU Biodesign Institute researcher Nick Stephanopoulos is one of several rising stars in regenerative medicine. In 2015, Stephanopoulos, along with Alex Green and Jeremy Mills, were recruited to the Biodesign Institutes Center for Molecular Design and Biomimetics (CMDB), directed by Hao Yan, a world-recognized leader in nanotechnology.

One of the things that that attracted me most to the ASU and the Biodesign CMDB was Haos vision to build a group of researchers that use biological molecules and design principles to make new materials that can mimic, and one day surpass, the most complex functions of biology, Stephanopoulos said.

I have always been fascinated by using biological building blocks like proteins, peptides and DNA to construct self-assembled structures, devices and materials, and the interdisciplinary and highly collaborative team in the CMDB is the ideal place to put this vision into practice.

Yans research center uses DNA and other basic building blocks to build their nanotechnology structures only at a scale 1,000 times smaller than the width of a human hair.

Theyve already used nanotechnology to build containers to specially deliver drugs to tissues, build robots to navigate a maze or nanowires for electronics.

To build a manufacturing industry at that tiny scale, their bricks and mortar use a colorful assortment of molecular Legos. Just combine the ingredients, and these building blocks can self-assemble in a seemingly infinite number of ways only limited by the laws of chemistry and physics and the creative imaginations of these budding nano-architects.

Learning from nature

The goal of the Center for Molecular Design and Biomimetics is to usenatures design rulesas an inspiration in advancing biomedical, energy and electronics innovation throughself-assembling moleculesto create intelligent materials for better component control and for synthesis intohigher-order systems, said Yan, who also holds the Milton Glick Chair in Chemistry and Biochemistry.

Prior to joining ASU, Stephanopoulos trained with experts in biological nanomaterials, obtaining his doctorate with the University of California Berkeleys Matthew Francis, and completed postdoctoral studies with Samuel Stupp at Northwestern University. At Northwestern, he was part of a team that developed a new category of quilt-like, self-assembling peptide and peptide-DNA biomaterials for regenerative medicine, with an emphasis in neural tissue engineering.

Weve learned from nature many of the rules behind materials that can self-assemble. Some of the most elegant complex and adaptable examples of self-assembly are found in biological systems, Stephanopoulos said.

Because they are built from the ground-up using molecules found in nature, these materials are also biocompatible and biodegradable, opening up brand-new vistas for regenerative medicine.

Stephanopoulos tool kit includes using proteins, peptides, lipids and nucleic acids like DNA that have a rich biological lexicon of self-assembly.

DNA possesses great potential for the construction of self-assembled biomaterials due to its highly programmable nature; any two strands of DNA can be coaxed to assemble to make nanoscale constructs and devices with exquisite precision and complexity, Stephanopoulos said.

Proof all in the design

During his time at Northwestern, Stephanopoulos worked on a number of projects and developed proof-of-concept technologies for spinal cord injury, bone regeneration and nanomaterials to guide stem cell differentiation.

Now, more recently, in a new studyin Nature Communications, Stephanopoulos and his colleague Ronit Freeman in the Stupp laboratory successfully demonstrated the ability to dynamically control the environment around stem cells, to guide their behavior in new and powerful ways.

In the new technology, materials are first chemically decorated with different strands of DNA, each with a unique code for a different signal to cells.

To activate signals within the cells, soluble molecules containing complementary DNA strands are coupled to short protein fragments, called peptides, and added to the material to create DNA double helices displaying the signal.

By adding a few drops of the DNA-peptide mixture, the material effectively gives a green light to stem cells to reproduce and generate more cells. In order to dynamically tune the signal presentation, the surface is exposed to a soluble single-stranded DNA molecule designed to grab the signal-containing strand of the duplex and form a new DNA double helix, displacing the old signal from the surface.

This new duplex can then be washed away, turning the signal off. To turn the signal back on, all that is needed is to now introduce a new copy of single-stranded DNA bearing a signal that will reattach to the materials surface.

One of the findings of this work is the possibility of using the synthetic material to signal neural stem cells to proliferate, then at a specific time selected by the scientist, trigger their differentiation into neurons for a while, before returning the stem cells to a proliferative state on demand.

One potential use of the new technology to manipulate cells could help cure a patient with neurodegenerative conditions like Parkinsons disease.

The patients own skin cells could be converted to stem cells using existing techniques. The new technology could help expand the newly converted stem cells back in the lab and then direct their growth into specific dopamine-producing neurons before transplantation back to the patient.

People would love to have cell therapies that utilize stem cells derived from their own bodies to regenerate tissue, Stupp said. In principle, this will eventually be possible, but one needs procedures that are effective at expanding and differentiating cells in order to do so. Our technology does that.

In the future, it might be possible to perform this process entirely within the body. The stem cells would be implanted in the clinic, encapsulated in the type of material described in the new work, and injected into a particular spot. Then the soluble peptide-DNA molecules would be given to the patient to bind to the material and manipulate the proliferation and differentiation of transplanted cells.

Scaling the barriers

One of the future challenges in this area will be to develop materials that can respond better to external stimuli and reconfigure their physical or chemical properties accordingly.

Biological systems are complex, and treating injury or disease will in many cases necessitate a material that can mimic the complex spatiotemporal dynamics of the tissues they are used to treat, Stephanopoulos said.

It is likely that hybrid systems that combine multiple chemical elements will be necessary; some components may provide structure, others biological signaling and yet others a switchable element to imbue dynamic ability to the material.

A second challenge, and opportunity, for regenerative medicine lies in creating nanostructures that can organize material across multiple length scales. Biological systems themselves are hierarchically organized: from molecules to cells to tissues, and up to entire organisms.

Consider that for all of us, life starts simple, with just a single cell. By the time we reach adulthood, every adult human body is its own universe of cells, with recent estimates of 37 trillion or so. The human brain alone has 100 billion cells or about the same number of cells as stars in the Milky Way galaxy.

But over the course of a life, or by disease, whole constellations of cells are lost due to the ravages of time or the genetic blueprints going awry.

Collaborative DNA

To overcome these obstacles, much more research funding and recruitment of additional talent to ASU will be needed to build the necessary regenerative medicine workforce.

Last year, Stephanopoulos research received a boost with funding from the U.S. Air Forces Young Investigator Research Program (YIP).

The Air Force Office of Scientific ResearchYIP award will facilitate Nicks research agenda in this direction, and is a significant recognition of his creativity and track record at the early stage of his careers, Yan said.

Theyll need this and more to meet the ultimate challenge in the development of self-assembled biomaterials and translation to clinical applications.

Buoyed by the funding, during the next research steps, Stephanopoulos wants to further expand horizons with collaborations from other ASU colleagues to take his research teams efforts one step closer to the clinic.

ASU and the Biodesign Institute also offer world-class researchers in engineering, physics and biology for collaborations, not to mention close ties with the Mayo Clinic or a number of Phoenix-area institutes so we can translate our materials to medically relevant applications, Stephanopoulos said.

There is growing recognition that regenerative medicine in the Valley could be a win-win for the area, in delivering new cures to patients and building, person by person, a brand-new medicinal manufacturing industry.

Stephanopoulos recent research was carried out at Stupps Northwesterns Simpson Querrey Institute for BioNanotechnology. The National Institute of Dental and Craniofacial Research of the National Institutes of Health (grant 5R01DE015920) provided funding for biological experiments, and the U.S. Department of Energy, Office of Science, Basic Energy Sciences provided funding for the development of the new materials (grants DE-FG01-00ER45810 and DE-SC0000989 supporting an Energy Frontiers Research Center on Bio-Inspired Energy Science (CBES)).

The paper is titled Instructing cells with programmable peptide DNA hybrids. Samuel I. Stupp is the senior author of the paper, and post-doctoral fellows Ronit Freeman and Nicholas Stephanopoulos are primary authors.

Read more here:

Bio-inspired Materials Give Boost to Regenerative Medicine - Bioscience Technology

Bio-inspired materials give boost to regenerative medicine – Medical Xpress

August 18, 2017 In a new studyin Nature Communications, Stephanopoulos and his colleague Ronit Freeman successfully demonstrated the ability to dynamically control the environment around stem cells, to guide their behavior in new and powerful ways. Credit: Northwestern University

What if one day, we could teach our bodies to self-heal like a lizard's tail, and make severe injury or disease no more threatening than a paper cut?

Or heal tissues by coaxing cells to multiply, repair or replace damaged regions in loved ones whose lives have been ravaged by stroke, Alzheimer's or Parkinson's disease?

Such is the vision, promise and excitement in the burgeoning field of regenerative medicine, now a major ASU initiative to boost 21st-century medical research discoveries.

ASU Biodesign Institute researcher Nick Stephanopoulos is one of several rising stars in regenerative medicine. In 2015, Stephanopoulos, along with Alex Green and Jeremy Mills, were recruited to the Biodesign Institute's Center for Molecular Design and Biomimetics (CMDB), directed by Hao Yan, a world-recognized leader in nanotechnology.

"One of the things that that attracted me most to the ASU and the Biodesign CMDB was Hao's vision to build a group of researchers that use biological molecules and design principles to make new materials that can mimic, and one day surpass, the most complex functions of biology," Stephanopoulos said.

"I have always been fascinated by using biological building blocks like proteins, peptides and DNA to construct self-assembled structures, devices and materials, and the interdisciplinary and highly collaborative team in the CMDB is the ideal place to put this vision into practice."

Yan's research center uses DNA and other basic building blocks to build their nanotechnology structuresonly at a scale 1,000 times smaller than the width of a human hair.

They've already used nanotechnology to build containers to specially deliver drugs to tissues, build robots to navigate a maze or nanowires for electronics.

To build a manufacturing industry at that tiny scale, their bricks and mortar use a colorful assortment of molecular Legos. Just combine the ingredients, and these building blocks can self-assemble in a seemingly infinite number of ways only limited by the laws of chemistry and physicsand the creative imaginations of these budding nano-architects.

Learning from nature

"The goal of the Center for Molecular Design and Biomimetics is to use nature's design rules as an inspiration in advancing biomedical, energy and electronics innovation through self-assembling molecules to create intelligent materials for better component control and for synthesis into higher-order systems," said Yan, who also holds the Milton Glick Chair in Chemistry and Biochemistry.

Prior to joining ASU, Stephanopoulos trained with experts in biological nanomaterials, obtaining his doctorate with the University of California Berkeley's Matthew Francis, and completed postdoctoral studies with Samuel Stupp at Northwestern University. At Northwestern, he was part of a team that developed a new category of quilt-like, self-assembling peptide and peptide-DNA biomaterials for regenerative medicine, with an emphasis in neural tissue engineering.

"We've learned from nature many of the rules behind materials that can self-assemble. Some of the most elegant complex and adaptable examples of self-assembly are found in biological systems," Stephanopoulos said.

Because they are built from the ground-up using molecules found in nature, these materials are also biocompatible and biodegradable, opening up brand-new vistas for regenerative medicine.

Stephanopoulos' tool kit includes using proteins, peptides, lipids and nucleic acids like DNA that have a rich biological lexicon of self-assembly.

"DNA possesses great potential for the construction of self-assembled biomaterials due to its highly programmable nature; any two strands of DNA can be coaxed to assemble to make nanoscale constructs and devices with exquisite precision and complexity," Stephanopoulos said.

Proof all in the design

During his time at Northwestern, Stephanopoulos worked on a number of projects and developed proof-of-concept technologies for spinal cord injury, bone regeneration and nanomaterials to guide stem cell differentiation.

Now, more recently, in a new study in Nature Communications, Stephanopoulos and his colleague Ronit Freeman in the Stupp laboratory successfully demonstrated the ability to dynamically control the environment around stem cells, to guide their behavior in new and powerful ways.

In the new technology, materials are first chemically decorated with different strands of DNA, each with a unique code for a different signal to cells.

To activate signals within the cells, soluble molecules containing complementary DNA strands are coupled to short protein fragments, called peptides, and added to the material to create DNA double helices displaying the signal.

By adding a few drops of the DNA-peptide mixture, the material effectively gives a green light to stem cells to reproduce and generate more cells. In order to dynamically tune the signal presentation, the surface is exposed to a soluble single-stranded DNA molecule designed to "grab" the signal-containing strand of the duplex and form a new DNA double helix, displacing the old signal from the surface.

This new duplex can then be washed away, turning the signal "off." To turn the signal back on, all that is needed is to now introduce a new copy of single-stranded DNA bearing a signal that will reattach to the material's surface.

One of the findings of this work is the possibility of using the synthetic material to signal neural stem cells to proliferate, then at a specific time selected by the scientist, trigger their differentiation into neurons for a while, before returning the stem cells to a proliferative state on demand.

One potential use of the new technology to manipulate cells could help cure a patient with neurodegenerative conditions like Parkinson's disease.

The patient's own skin cells could be converted to stem cells using existing techniques. The new technology could help expand the newly converted stem cells back in the laband then direct their growth into specific dopamine-producing neurons before transplantation back to the patient.

"People would love to have cell therapies that utilize stem cells derived from their own bodies to regenerate tissue," Stupp said. "In principle, this will eventually be possible, but one needs procedures that are effective at expanding and differentiating cells in order to do so. Our technology does that."

In the future, it might be possible to perform this process entirely within the body. The stem cells would be implanted in the clinic, encapsulated in the type of material described in the new work, and injected into a particular spot. Then the soluble peptide-DNA molecules would be given to the patient to bind to the material and manipulate the proliferation and differentiation of transplanted cells.

Scaling the barriers

One of the future challenges in this area will be to develop materials that can respond better to external stimuli and reconfigure their physical or chemical properties accordingly.

"Biological systems are complex, and treating injury or disease will in many cases necessitate a material that can mimic the complex spatiotemporal dynamics of the tissues they are used to treat," Stephanopoulos said.

It is likely that hybrid systems that combine multiple chemical elements will be necessary; some components may provide structure, others biological signaling and yet others a switchable element to imbue dynamic ability to the material.

A second challenge, and opportunity, for regenerative medicine lies in creating nanostructures that can organize material across multiple length scales. Biological systems themselves are hierarchically organized: from molecules to cells to tissues, and up to entire organisms.

Consider that for all of us, life starts simple, with just a single cell. By the time we reach adulthood, every adult human body is its own universe of cells, with recent estimates of 37 trillion or so. The human brain alone has 100 billion cells or about the same number of cells as stars in the Milky Way galaxy.

But over the course of a life, or by disease, whole constellations of cells are lost due to the ravages of time or the genetic blueprints going awry.

Collaborative DNA

To overcome these obstacles, much more research funding and recruitment of additional talent to ASU will be needed to build the necessary regenerative medicine workforce.

Last year, Stephanopoulos' research received a boost with funding from the U.S. Air Force's Young Investigator Research Program (YIP).

"The Air Force Office of Scientific Research YIP award will facilitate Nick's research agenda in this direction, and is a significant recognition of his creativity and track record at the early stage of his careers," Yan said.

They'll need this and more to meet the ultimate challenge in the development of self-assembled biomaterials and translation to clinical applications.

Buoyed by the funding, during the next research steps, Stephanopoulos wants to further expand horizons with collaborations from other ASU colleagues to take his research team's efforts one step closer to the clinic.

"ASU and the Biodesign Institute also offer world-class researchers in engineering, physics and biology for collaborations, not to mention close ties with the Mayo Clinic or a number of Phoenix-area institutes so we can translate our materials to medically relevant applications," Stephanopoulos said.

There is growing recognition that regenerative medicine in the Valley could be a win-win for the area, in delivering new cures to patients and building, person by person, a brand-new medicinal manufacturing industry.

Explore further: New technology to manipulate cells could help treat Parkinson's, arthritis, other diseases

More information: Ronit Freeman et al. Instructing cells with programmable peptide DNA hybrids, Nature Communications (2017). DOI: 10.1038/ncomms15982

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Bio-inspired materials give boost to regenerative medicine - Medical Xpress

Family medicine residents worked their way to Victoria – Victoria Advocate


Victoria Advocate
Family medicine residents worked their way to Victoria
Victoria Advocate
Dr. Jeff Mistroff, of Coral Springs, Fla., earned a bachelor's degree in microbiology/molecular biology from the University of Central Florida and an MBA with a health care management concentration from Davenport University. He then completed his ...

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Family medicine residents worked their way to Victoria - Victoria Advocate

Spotlight Innovation Enters into Sponsored Research Agreement with Indiana University to Develop New Therapies for … – Markets Insider

URBANDALE, Iowa, Aug. 16, 2017 /PRNewswire/ --Spotlight Innovation Inc. (OTCQB: STLT) today announced that the Company has entered into a Sponsored Research Agreement with Indiana University to support research directed by Elliot Androphy, M.D., aimed at developing safe and effective drugs to treat patients with spinal muscular atrophy (SMA). Dr. Androphy is a member of Spotlight Innovation's Scientific Advisory Board and a co-inventor of STL-182, the Company's lead product candidate for SMA.

Geoffrey Laff, Ph.D., Spotlight Innovation's Senior Vice President of Business Development, commented, "Dr. Androphy is a prolific researcher and highly-respected thought leader. We are privileged to work with him to develop novel therapies for SMA."

Dr. Androphy is the Chair of the Department of Dermatology of Indiana University School of Medicine and has published widely in high-impact journals including Science, Nature, EMBO Molecular Medicine, Human Molecular Genetics, Journal of Virology, and Molecular Cell. He served as Vice Chair for Research of the Department of Medicine and Director of the M.D./Ph.D. Program at the University of Massachusetts Medical School where his lab characterized the disease-causing mechanism of alternative splicing of the SMN2 gene. At Indiana University School of Medicine, Dr. Androphy has used a novel, cell-based high throughput screen for compounds that increase levels of the SMN protein. This work has led to the identification of pre-clinical drug candidates for SMA.

About Spotlight Innovation Inc.

Spotlight Innovation Inc. (OTCQB: STLT) identifies and acquires rights to innovative, proprietary technologies designed to address unmet medical needs, with an emphasis on rare, emerging and neglected diseases. To find and evaluate unique opportunities, we leverage our extensive relationships with leading scientists, academic institutions and other sources. We provide value-added development capability to accelerate development progress. Whenscientifically significantbenchmarkshave been achieved, we will endeavor to partner with proven market leaders via sale, out-license or strategic alliance. For more information, visit http://www.spotlightinnovation.com or follow us on http://www.twitter.com/spotlightinno.

Forward-Looking Statements

Statements in this press release that are not purely historical are forward-looking statements. Forward-looking statements herein include statements regarding Spotlight Innovation's efforts to develop and commercialize various product candidates, including STL-182, and to achieve its stated benchmarks. Actual outcomes and actual results could differ materially from those in such forward-looking statements. Factors that could cause actual results to differ materially include risks and uncertainties, such as: the inability to finance the planned development of STL-182; the inability to hire appropriate staff to develop STL-182; unforeseen technical difficulties in developing STL-182; the inability to obtain regulatory approval for human use; competitors' therapies proving to be more effective, cheaper or otherwise more preferable; or, the inability to market a product. All of which could, among other things, delay or prevent product release, as well as other factors expressed from time to time in Spotlight Innovation's periodic filings with the Securities and Exchange Commission (SEC). As a result, this press release should be read in conjunction with Spotlight Innovation's periodic filings with the SEC. The forward-looking statements contained herein are made only as of the date of this press release and Spotlight Innovation undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

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Spotlight Innovation Enters into Sponsored Research Agreement with Indiana University to Develop New Therapies for ... - Markets Insider

A new method of 3D printing living tissues – 3D Printing Progress

Scientists at the University of Oxford have developed a new method to 3D-print laboratory-grown cells to form living structures. The approach could revolutionise regenerative medicine, enabling the production of complex tissues and cartilage that would potentially support, repair or augment diseased and damaged areas of the body.

Printing high-resolution living tissues is hard to do, as the cells often move within printed structures and can collapse on themselves. But, led by Professor Hagan Bayley, Professor of Chemical Biology in Oxford's Department of Chemistry, the team devised a way to produce tissues in self-contained cells that support the structures to keep their shape.

The cells were contained within protective nanolitre droplets wrapped in a lipid coating that could be assembled, layer-by-layer, into living structures. Producing printed tissues in this way improves the survival rate of the individual cells, and allowed the team to improve on current techniques by building each tissue one drop at a time to a more favourable resolution.

To be useful, artificial tissues need to be able to mimic the behaviours and functions of the human body. The method enables the fabrication of patterned cellular constructs, which, once fully grown, mimic or potentially enhance natural tissues.

Dr Alexander Graham, lead author and 3D Bioprinting Scientist at OxSyBio (Oxford Synthetic Biology), said: "We were aiming to fabricate three-dimensional living tissues that could display the basic behaviours and physiology found in natural organisms. To date, there are limited examples of printed tissues, which have the complex cellular architecture of native tissues. Hence, we focused on designing a high-resolution cell printing platform, from relatively inexpensive components, that could be used to reproducibly produce artificial tissues with appropriate complexity from a range of cells including stem cells".

The researchers hope that, with further development, the materials could have a wide impact on healthcare worldwide. Potential applications include shaping reproducible human tissue models that could take away the need for clinical animal testing.

Over the coming months they will work to develop new complementary printing techniques, that allow the use of a wider range of living and hybrid materials, to produce tissues at industrial scale. Dr Sam Olof, Chief Technology Officer at OxSyBio, said: "There are many potential applications for bioprinting and we believe it will be possible to create personalised treatments by using cells sourced from patients to mimic or enhance natural tissue function. In the future, 3D bio-printed tissues maybe also be used for diagnostic applications - for example, for drug or toxin screening."

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A new method of 3D printing living tissues - 3D Printing Progress

Using barcodes to trace cell development – Medical Xpress

August 16, 2017 Credit: CC0 Public Domain

How do the multiple different cell types in the blood develop? Scientists have been pursuing this question for a long time. According to the classical model, different developmental lines branch out like in a tree. The tree trunk is composed of stem cells and the branches are made up of various types of progenitor cells that can give rise to a number of distinct cell types. Then it further branches off into the specialized blood cells, i.e., red blood cells, blood platelets and various types of white blood cells that are part of the immune system. In recent years, however, doubts about this model have arisen.

Hans-Reimer Rodewald, a scientist at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, and his co-workers wanted to capture the dynamic events in blood cell formation instead of merely taking snapshots. In close collaboration with a research team led by systems biologist Thomas Hfer, the scientists have developed a new technology that enables them to precisely follow the developmental tracks of cells. To this end, they label stem cells with a kind of genetic barcode in order to be able to clearly identify their offspring later.

"Genetic barcodes have been developed and applied before, but they were based on methods that can also change cellular properties," Rodewald said. "Our barcodes are different: They can be induced tissue-specifically and directly in the genome of mice - without influencing the animals' physiological development." The basis of the new technology is the so-called Cre/loxP system that is used to rearrange or remove specially labeled DNA segments.

Weike Pei und Thorsten Feyerabend in Rodewald's team bred mice whose genomes exhibit the basic elements of the barcode. At a selected site, where no genes are encoded, it contains nine small DNA fragments from a plant called Arabidopsis thaliana. These elements are flanked by ten genetic cutting sites called IoxP sites. By administering a pharmacological agent, the matching molecular scissors called "Cre" can be activated in the animals' hematopoietic stem cells. Then code elements are randomly rearranged or cut out. "This genetic random DNA barcode generator can generate up to 1.8 million genetic barcodes and we can identify the codes that arise only once in an experiment," Hfer said.

"The mice then do the rest of the work," said Rodewald. When these specially labeled hematopoietic stem cells divide and mature, the barcodes are preserved. In collaboration with the Max Delbrck Center for Molecular Medicine, the researchers have performed comprehensive barcode analyses in order to trace an individual blood cell back to the stem cell from which it originates.

These analyses have revealed that two large developmental branches start out from the hematopoietic stem cells of the mice: In one branch, T cells and B cells of the immune system develop; in the other, red blood cells as well as various other types of white blood cells such as granulocytes and monocytes form. All these cell types can arise from a single stem cell. "Our findings show that the classical model of a hierarchical developmental tree that starts from multipotent stem cells holds true for hematopoiesis," Rodewald emphasized.

The system developed by the Heidelberg researchers can also be used for other purposes besides studying blood cell development. This strategy can basically be applied in any tissue. In the future, it might also be used for experimentally tracing the origin of leukemias and other cancers.

Explore further: Live assessment of blood formation

More information: Weike Pei et al, Polylox barcoding reveals haematopoietic stem cell fates realized in vivo, Nature (2017). DOI: 10.1038/nature23653

Since ancient times, humankind has been aware of how important blood is to life. Naturalists speculated for thousands of years on the source of the body's blood supply. For several centuries, the liver was believed to be ...

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Using barcodes to trace cell development - Medical Xpress

Yenepoya University to offer biotech skill enhancement programme – Hindu Business Line

Mangaluru, August 16:

The Centre for Systems Biology and Molecular Medicine at Yenepoya University in Mangaluru has been awarded the Biotechnology Skill Enhancement Programme (BiSEP) by the Karnataka Biotechnology and Information Technology Services (KBITS).

Addressing presspersons in Mangaluru on Wednesday, T.S. Keshava Prasad, Deputy Director of the Centre for Systems Biology and Molecular Medicine, said the centre has been awarded the BiSEP to conduct a one-year postgraduate diploma in multiomics technology. (Multiomics is an interdisciplinary subject that includes genomics, proteomics, metabolomics and proteogenomics.)

He said Yenepoya University is the only centre to offer BiSEP in multiomics technology. The centre has facilities and experts in this technology to undertake such a training programme.

Candidates for BiSEP - postgraduate diploma programme - will be selected based on their performance in the Karnataka Biotechnology Aptitude Test to be held in September. Students enrolled in the programme will be provided fellowship of Rs 10,000 a month during the course.

He said 50 per cent of the tuition fee for Karnataka students will be paid by the state government.

Students will undergo a six-month hands-on training programme in different omics platforms at the Centre for Systems Biology and Molecular Medicine. This will be followed by a six-month internship.

He said graduates and postgraduates in the field of life sciences would be equipped with necessary employable skills under BiSEP. This will help make them industry-ready in the field of genomic, proteomic and metabolomic technologies. This programme will enable supply of skilled manpower required by multinational biotechnology and pharmaceutical companies, he added.

(This article was published on August 16, 2017)

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Yenepoya University to offer biotech skill enhancement programme - Hindu Business Line

Spotlight Innovation Enters into Sponsored Research Agreement with Indiana University to Develop New Therapies for … – PR Newswire (press release)

Geoffrey Laff, Ph.D., Spotlight Innovation's Senior Vice President of Business Development, commented, "Dr. Androphy is a prolific researcher and highly-respected thought leader. We are privileged to work with him to develop novel therapies for SMA."

Dr. Androphy is the Chair of the Department of Dermatology of Indiana University School of Medicine and has published widely in high-impact journals including Science, Nature, EMBO Molecular Medicine, Human Molecular Genetics, Journal of Virology, and Molecular Cell. He served as Vice Chair for Research of the Department of Medicine and Director of the M.D./Ph.D. Program at the University of Massachusetts Medical School where his lab characterized the disease-causing mechanism of alternative splicing of the SMN2 gene. At Indiana University School of Medicine, Dr. Androphy has used a novel, cell-based high throughput screen for compounds that increase levels of the SMN protein. This work has led to the identification of pre-clinical drug candidates for SMA.

About Spotlight Innovation Inc.

Spotlight Innovation Inc. (OTCQB: STLT) identifies and acquires rights to innovative, proprietary technologies designed to address unmet medical needs, with an emphasis on rare, emerging and neglected diseases. To find and evaluate unique opportunities, we leverage our extensive relationships with leading scientists, academic institutions and other sources. We provide value-added development capability to accelerate development progress. Whenscientifically significantbenchmarkshave been achieved, we will endeavor to partner with proven market leaders via sale, out-license or strategic alliance. For more information, visit http://www.spotlightinnovation.com or follow us on http://www.twitter.com/spotlightinno.

Forward-Looking Statements

Statements in this press release that are not purely historical are forward-looking statements. Forward-looking statements herein include statements regarding Spotlight Innovation's efforts to develop and commercialize various product candidates, including STL-182, and to achieve its stated benchmarks. Actual outcomes and actual results could differ materially from those in such forward-looking statements. Factors that could cause actual results to differ materially include risks and uncertainties, such as: the inability to finance the planned development of STL-182; the inability to hire appropriate staff to develop STL-182; unforeseen technical difficulties in developing STL-182; the inability to obtain regulatory approval for human use; competitors' therapies proving to be more effective, cheaper or otherwise more preferable; or, the inability to market a product. All of which could, among other things, delay or prevent product release, as well as other factors expressed from time to time in Spotlight Innovation's periodic filings with the Securities and Exchange Commission (SEC). As a result, this press release should be read in conjunction with Spotlight Innovation's periodic filings with the SEC. The forward-looking statements contained herein are made only as of the date of this press release and Spotlight Innovation undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

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Spotlight Innovation Enters into Sponsored Research Agreement with Indiana University to Develop New Therapies for ... - PR Newswire (press release)

New Version of CRISPR Corrects RNA Defects Linked to … – Technology Networks

These are muscle cells from a patient with myotonic dystrophy type I, untreated (left) and treated with the RNA-targeting Cas9 system (right). The MBNL1 protein is in green, repetitive RNA in red and the cells nucleus in blue. MBNL1 is an important RNA-binding protein and its normal function is disrupted when it binds repetitive RNA. In the treated cells on the right, MBNL1 is released from the repetitive RNA. Credit: UCSD

Until recently, the CRISPR-Cas9 gene editing technique could only be used to manipulate DNA. In a 2016 study, University of California San Diego School of Medicine researchers repurposed the technique to track RNA in live cells in a method called RNA-targeting Cas9 (RCas9). In a new study, published August 10 in Cell, the team takes RCas9 a step further: they use the technique to correct molecular mistakes that lead to microsatellite repeat expansion diseases, which include myotonic dystrophy types 1 and 2, the most common form of hereditary ALS, and Huntington's disease.

This is exciting because were not only targeting the root cause of diseases for which there are no current therapies to delay progression, but weve re-engineered the CRISPR-Cas9 system in a way thats feasible to deliver it to specific tissues via a viral vector, said senior author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine.

While DNA is like the architects blueprint for a cell, RNA is the engineers interpretation of the blueprint. In the central dogma of life, genes encoded in DNA in the nucleus are transcribed into RNA and RNAs carry the message out into the cytoplasm, where they are translated to make proteins.

Microsatellite repeat expansion diseases arise because there are errant repeats in RNA sequences that are toxic to the cell, in part because they prevent production of crucial proteins. These repetitive RNAs accumulate in the nucleus or cytoplasm of cells, forming dense knots, called foci.

In this proof-of-concept study, Yeos team used RCas9 to eliminate the problem-causing RNAs associated with microsatellite repeat expansion diseases in patient-derived cells and cellular models of the diseases in the laboratory.

Normally, CRISPR-Cas9 works like this: researchers design a guide RNA to match the sequence of a specific target gene. The RNA directs the Cas9 enzyme to the desired spot in the genome, where it cuts DNA. The cell repairs the DNA break imprecisely, thus inactivating the gene, or researchers replace the section adjacent to the cut with a corrected version of the gene. RCas9 works similarly but the guide RNA directs Cas9 to an RNA molecule instead of DNA.

The researchers tested the new RCas9 system on microsatellite repeat expansion disease RNAs in the laboratory. RCas9 eliminated 95 percent or more of the RNA foci linked to myotonic dystrophy type 1 and type 2, one type of ALS and Huntington's disease. The approach also eliminated 95 percent of the aberrant repeat RNAs in myotonic dystrophy patient cells cultured in the laboratory.

Another measure of success centered on MBNL1, a protein that normally binds RNA, but is sequestered away from hundreds of its natural RNA targets by the RNA foci in myotonic dystrophy type 1. When the researchers applied RCas9, they reversed 93 percent of these dysfunctional RNA targets in patient muscle cells, and the cells ultimately resembled healthy control cells.

While this study provides the initial evidence that the approach works in the laboratory, there is a long way to go before RCas9 could be tested in patients, Yeo explained.

One bottleneck is efficient delivery of RCas9 to patient cells. Non-infectious adeno-associated viruses are commonly used in gene therapy, but they are too small to hold Cas9 to target DNA. Yeos team made a smaller version of Cas9 by deleting regions of the protein that were necessary for DNA cleavage, but dispensable for binding RNA.

The main thing we dont know yet is whether or not the viral vectors that deliver RCas9 to cells would elicit an immune response, he said. Before this could be tested in humans, we would need to test it in animal models, determine potential toxicities and evaluate long-term exposure.

To do this, Yeo and colleagues launched a spin-out company called Locana to handle the preclinical steps required for moving RCas9 from the lab to the clinic for RNA-based diseases, such as those that arise from microsatellite repeat expansions.

We are really excited about this work because we not only defined a new potential therapeutic mechanism for CRISPR-Cas9, we demonstrated how it could be used to treat an entire class of conditions for which there are no successful treatment options, said David Nelles, PhD, co-first author of the study with Ranjan Batra, PhD, both postdoctoral researchers in Yeos lab.

There are more than 20 genetic diseases caused by microsatellite expansions in different places in the genome, Batra said. Our ability to program the RCas9 system to target different repeats, combined with low risk of off-target effects, is its major strength.

This article has been republished frommaterialsprovided by University of California, San Diego. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference

Batra, R., Nelles, D. A., Pirie, E., Blue, S. M., Marina, R. J., Wang, H., ... & Aigner, S. (2017). Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9. Cell.

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Cancer Treatment Centers of America and Foundation Medicine Join Forces to Advance Precision Cancer Treatment – Markets Insider

CAMBRIDGE, Mass., Aug. 15, 2017 /PRNewswire/ --Cancer Treatment Centers of America (CTCA) and Foundation Medicine today announced a new element to their longstanding partnership to increase awareness of advancements in genomic testing and precision medicine in oncology. The educational initiative directed toward physicians, other caregivers and patients will highlight the importance of integrating comprehensive genomic testing of solid tumors early in an individual's care plan as a model to inform personalized care and improve clinical outcomes for individuals with cancer.

"Precision cancer treatment using advanced genomic testing is changing the science of cancer care," said Maurie Markman, M.D., President of Medicine & Science at CTCA. "As oncologists, we have an obligation to the patients we serve to keep pace with, and, whenever possible, lead the way in the application of the latest diagnostic tools that may help inform treatment decisions. Our partnership with Foundation Medicine empowers our physicians to customize treatment plans according to the individual patient's clinical profile right down to the molecular level, and therefore furnish care in a much more comprehensive and effective manner."

The partnership brings together CTCA, a national network of five cancer treatment hospitals at the forefront of delivering precision cancer treatment to address individual patients' unique treatment needs, and Foundation Medicine, a leader in molecular information that offers a suite of comprehensive genomic profiling (CGP) assays that identifies the molecular alterations in an individual's cancer and matches them with potentially relevant targeted therapies, including immunotherapies.

Through their shared patient-centered philosophy, CTCA and Foundation Medicine will educate the medical community about the successful approach CTCA is using to incorporate FoundationOne for solid tumors into clinical care. Specifically, the educational initiative will feature several patients with cancer, chronicling each person's journey from cancer diagnosis to tumor profiling to treatment. Through this case-based approach, the program aims to provide insights into precision medicine treatment approaches based on an individual's unique cancer, including the selection of targeted therapies, appropriate clinical trials and responses to immunotherapy.

"Precision medicine, and a move to a more personalized, targeted approach to cancer care, is becoming ever more ubiquitous as the published data continues to validate this approach as leading to better clinical outcomes for patients," said Vincent Miller, M.D., Chief Medical Officer for Foundation Medicine. "As such, it's critical that every stakeholder in a patient's care planphysician, patient and care teamis knowledgeable about the benefits of genomic profiling, and importantly, that they have the right tools at the ready to implement such an approach. We applaud CTCA leadership in this area and we're delighted to collaborate with them on this educational initiative."

To learn more about genomics and precision cancer treatment, visit cancercenter.com. To learn more about genomic testing and FoundationOne, visit FoundationMedicine.com.

About Cancer Treatment Centers of AmericaCancer Treatment Centers of America Global, Inc. (CTCA), headquartered in Boca Raton, Fla., is a national network of five hospitals that serves adult patients who are fighting cancer. CTCA offers an integrative approach to care that combines advancements in genomic testing and precision cancer treatment, surgery, radiation, immunotherapy and chemotherapy, with evidence-informed supportive therapies designed to help patients physically and emotionally by enhancing their quality of life while managing side effects both during and after treatment. CTCA serves patients from around the world at its hospitals in Atlanta, Chicago, Philadelphia, Phoenix and Tulsa. Reflecting our patient-centered approach to cancer care, our patient satisfaction scores consistently rank among the highest in the country for cancer care providers, and CTCA is also rated one of the most admired hospital systems in the country in national consumer surveys. For more information, visit cancercenter.com, Facebook.com/cancercenter and Twitter.com/cancercenter.

About Foundation Medicine Foundation Medicine(NASDAQ:FMI) is a molecular information company dedicated to a transformation in cancer care in which treatment is informed by a deep understanding of the genomic changes that contribute to each patient's unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patient's cancer and match them with relevant targeted therapies, immunotherapies and clinical trials.Foundation Medicine'smolecular information platform aims to improve day-to-day care for patients by serving the needs of clinicians, academic researchers and drug developers to help advance the science of molecular medicine in cancer. For more information, please visithttp://www.FoundationMedicine.comor followFoundation Medicineon Twitter (@FoundationATCG). Foundation Medicineand FoundationOne are registered trademarks ofFoundation Medicine, Inc.

Cautionary Note Regarding Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the objectives of any educational initiatives between CTCA and Foundation Medicine; the importance of integrating comprehensive genomic testing of solid tumors early in an individual's care plan to improve clinical outcomes for individuals with cancer; and the value and performance capabilities of Foundation Medicine's comprehensive genomic profiling assays. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include the risk thateducational initiatives are not developed or launched in the anticipated manner; Foundation Medicine'sCGP andservices will not be able to identify genomic alterations in the same manner as prior clinical data or prior experience; and the risks described under the caption "Risk Factors" inFoundation Medicine'sAnnual Report on Form 10-K for the year endedDecember 31, 2016, which is on file with theSecurities and Exchange Commission, as well as other risks detailed inFoundation Medicine'ssubsequent filings with theSecurities and Exchange Commission.All information in this press release is as of the date of the release, andFoundation Medicineundertakes no duty to update this information unless required by law.

Contact: Michael Myers Cancer Treatment Centers of America rel="nofollow">michael.myers@ctca-hope.com 561-923-3179

Lee-Ann Murphy Foundation Medicine 617-245-3077 rel="nofollow">pr@foundationmedicine.com

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Circular RNA Linked to Brain Function – Technology Networks

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the current issue of Science, Nikolaus Rajewsky and his team at the Berlin Institute of Medical Systems Biology (BIMSB) of the Max Delbrck Center for Molecular Medicine in the Helmholtz Association (MDC), as well as other collaborators within the MDC and Charit, present data that for the first time link a circular RNA to brain function.

RNA is much more than the mundane messenger between DNA and the protein it encodes. Indeed, there are several different kinds of non-coding RNA molecules. They can be long non-coding RNAs (lncRNAs) or short regulatory RNAs (miRs); they can interfere with protein production (siRNAs) or help make it possible (tRNAs). In the past 20 years, scientists have discovered some two dozen RNA varieties that form intricate networks within the molecular microcosm. The most enigmatic among them are circRNAs, an unusual class of RNAs whose heads are connected to their tails to form a covalently closed ring. These structures had for decades been dismissed as a rare, exotic RNA species. In fact, the opposite is true. Current RNA-sequencing analyses have revealed that they are a large class of RNA, which is highly expressed in brain tissues.

Thousands of circular RNAs exist in nematode worms, mice and humans

In 2013, two pioneering studies that characterized circular RNAs appeared in the journal Nature, one of them by Nikolaus Rajewsky and his team. Intriguingly, most circular RNAs are unusually stable, floating in the cytoplasm for hours and even days on end. The systems biologists proposed that at least sometimes circRNAs serve gene regulation. Cdr1as, a large single-stranded RNA loop that is 1,500 nucleotides around, might act as a sponge for microRNAs. For example, it offers more than 70 binding sites for a microRNA called miR-7. MicroRNAs are short RNA molecules that typically bind to complementary sequences in messenger RNAs, thereby controlling the amounts of specific proteins produced by cells.

Additionally, Rajewsky and his collaborators mined databases and discovered thousands of different circRNAs in nematode worms, mice and humans. Most of them were highly conserved throughout evolution. We had found a parallel universe of unexplored RNAs, says Rajewsky. Since publication the field has exploded; hundreds of new studies have been carried out.

Understanding a circle that is mostly present in excitatory neurons

For the current paper in Science, the systems biologists teamed up with Carmen Birchmeiers lab at the MDC to reconsider Cdr1as. This particular circle can be found in excitatory neurons but not in glial cells, says Monika Piwecka, one of the first authors of the paper and coordinator of most of the experiments. In brain tissues of mice and humans, there are two microRNAs called miR-7 and miR-671 that bind to it. In a next step, Rajewsky and his collaborators selectively deleted the circRNA Cdr1as in mice using the genome editing technology CRISPR/Cas9. In these animals, the expression of most microRNAs in four studied brain regions remained unperturbed. However, miR-7 was downregulated and miR-671 upregulated. These changes were post-transcriptional, consistent with the idea that Cdr1as usually interacts with these microRNAs in the cytoplasm.

This indicates that Cdr1as usually stabilizes or transports miR-7 in neurons by sponging them up, while miR-167 might serve to regulate levels of this particular circular RNA, says Rajewsky. If microRNA floated in the cytoplasm without binding anywhere, it would get broken down as waste. The circle would prevent that and also carry it to new places like the synapses. He adds: Maybe we should think about Cdr1as not as a sponge but as a boat. It prevents its passengers from drowning and also moves on to new ports.

The changes in microRNA concentration had dramatic effects on the mRNA and proteins produced by nerve cells, especially for a group called immediate early genes. They are part of the first wave of responses when stimuli are presented to neurons. Also affected were messenger RNAs that encode proteins involved in the maintenance of the animals sleep-wake cycles.

Cdr1as modulates synaptic responses

Using single-cell electrophysiology, Charit-researcher Christian Rosenmund observed that spontaneous vesicle release at the synapse happened twice as often. The synaptic responses to two consecutive stimuli were also altered. Additional behavioral analyses performed at the MDC mirrored these findings. Even though the mice appeared normal in many ways, they were unable to tune down their responses to external signals such as noises. Similar disruptions in pre-pulse inhibition have been noted in patients suffering from schizophrenia or other psychiatric diseases.

It is an everyday experience how much we depend on this filtering function: When a loud noise suddenly disturbs the quiet atmosphere of a library, you cannot avoid being alarmed. The same bang, however, will seem much less threatening next to a construction site. In this instance, the brain has had the chance to process previous noises and filter out unnecessary information. Therefore, the startle reflex is dampened (pre-pulse inhibition). This basic brain function that allows healthy animals and people to temporarily adapt to a strong stimulus and avoid information overload has now been linked to Cdr1as.

Functionally, our data suggest that Cdr1as and its direct interactions with microRNAs are important for sensorimotor gating and synaptic transmission, says Nikolaus Rajewsky. More generally, since the brain is an organ with exceptionally high and diverse expression of circular RNAs, we believe that our data suggest the existence of a previously unknown layer of biological functions carried out by these circles.

Reference

Piwecka, M., Glaar, P., Hernandez-Miranda, L. R., Memczak, S., Wolf, S. A., Rybak-Wolf, A., ... & Trimbuch, T. (2017). Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science, eaam8526.

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Circular RNA Linked to Brain Function - Technology Networks

Clinical trial uses a genetically engineered virus to fight cancer – Medical Xpress

August 15, 2017 Dr. Steven Powell. Credit: Sanford Health

Sanford Health is the first site in the United States to launch a clinical trial using a genetically-engineered virus that aims to destroy therapy-resistant tumors.

The Phase I immunotherapy trial is for those ages 18 and older with metastatic solid tumors that have not responded to standard treatments. The treatment injects an oncolytic (cancer-destroying) virusvesicular stomatitis virus (VSV)into the tumor. The virus is engineered to grow in cancer cells, destroy these tumors, and then spread to other cancer sites. During this process, it recruits the immune system to the area with the goal of triggering an immune response.

The virus, commonly known as VSV, can infect cattle, but it rarely causes serious infections in humans.

The virus is genetically altered by adding two genes. The first gene is a human interferon beta gene, which is a natural anti-viral protein. This protects the normal, healthy cells from being infected, while still allowing the virus to work against cancer cells.

The second gene makes the NIS protein found in the thyroid gland, which allows the researchers to track the virus as it spreads to tumor sites. Vyriad, a biopharmaceutical company in Rochester, Minnesota, developed this technology and is led by Stephen Russell, M.D., Ph.D., a professor of molecular medicine at the Mayo Clinic and an expert in oncolytic virus therapy.

"Oncolytic viruses are the next wave of promising cancer immunotherapy treatments," says Dr. Steven Powell, a medical oncologist with the Sanford Cancer Center in Sioux Falls, S.D., who collaborated with Vyriad on the development of this clinical trial. "We are very excited about using VSV as researchers have seen promising results using other similar viruses, such as the polio virus, in early clinical trials."

Dr. Shannon Peck, an interventional radiologist at Sanford with experience in interventional therapeutics, oversees the viral injection procedures. Enrollees in the trial are given a one-time injection and then are followed for 43 days to evaluate for safety and clinical benefit. To ensure safety during this period, other anti-cancer therapies cannot be used. However, after this 43-day period, chemotherapy, immunotherapy or targeted therapy can be restarted.

Sanford Health is the first in the nation to launch the Vyriad solid tumor oncolytic virus clinical trial. Call 1-877-SURVIVAL to learn more or to see if you qualify.

Explore further: First study of Oncolytic HSV-1 in children and young adults with cancer indicates safety, tolerability

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A New Gene Editing Technique Could Finally Allow Us to Treat ALS – Futurism

In BriefResearchers from UC San Diego's School of Medicine have testeda modified CRISPR-Cas9 technique designed to target RNA instead ofDNA. Rcas9 could potentially improve the lives of patients withALS, Huntington's disease, or myotonic dystrophy by delaying theprogression of their disorders. Editing RNA

The most efficient and effective gene-editing tool in use today is CRISPR-Cas9. Just this year, researchers have successfully used it fora wide variety of experiments, from modifying garden vegetables to encoding a GIF in bacterial DNA. Most recently, the tool was used to remove a genetic disease from a human embryo.

Although undeniably powerful, CRISPR-Cas9 does have its limitations; it can only target DNA. To extend its capabilities to includeRNA editing, researchers from the University of California San Diego (UCSD) School of Medicinedeveloped amodification of CRISPR, and theyre calling their toolRNA-targeting Cas9 (RCas9).

In a study published in Cell, the UCSD team tested their technique by correcting the kinds of molecular mistakes that cause people to develop microsatellite repeat expansion diseases, such ashereditary amyotrophic lateral sclerosis (ALS)and Huntingtons disease.

During standard CRISPR-CAs9 gene editing, a guide RNA is instructed to deliver a Cas9 enzyme to a specific DNA molecule. The researchers from UCSD instead instructed it to target an RNA molecule.

Tests conducted in the laboratory showed that RCas9 removed 95 percent ofproblem-causing RNA for myotonic dystrophy types 1 and 2, Huntingtons disease, and one type of ALS. The technique also reversed 93 percent of the dysfunctional RNA targets in the muscle cells of patients with myotonic dystrophy type 1, resulting in healthier cells.

This is exciting because were not only targeting the root cause of diseases for which there are no current therapies to delay progression, but weve re-engineered the CRISPR-Cas9 system in a way thats feasible to deliver it to specific tissues via a viral vector, senior author Gene Yeo, a cellular and molecular medicine professor at UCSD School of Medicine, explained in a press release.

Across the globe, an estimated 450,000 patients are said to be living with ALS. Roughly 30,000 of those are from the U.S. where 5,600 people are diagnosed with the diseases every year. The exact number of Huntingtons disease cases, however, isnt quite as easy to pin down. One estimate says that around 30,000 Americans display symptoms of it, while more than 200,000 are at risk.

Regardless of the exact numbers, these two neurological diseases clearly affect a significant number of people. This prevalence and the absence of a known curemakes the UCSD teams research all the more relevant. Even more exciting is the fact that the same kinds of RNA mutations targeted by this study are known to cause more than 20 other genetic diseases.

Our ability to program the RCas9 system to target different repeats, combined with low risk of off-target effects, is its major strength, co-first author of the study Ranjan Batra said in the UCSD press release.

However, the researchers do know that what theyve accomplished is just a first step. While RCas9 works in a lab, they still have to figure out how it will fare when tested in actual patients.

The main thing we dont know yet is whether or not the viral vectors that deliver RCas9 to cells would elicit an immune response, explained Yeo. Before this could be tested in humans, we would need to test it in animal models, determine potential toxicities, and evaluate long-term exposure.

Ultimately, while RCas9 couldnt exactly deliver a cure, it could potentially extend patients healthy years. For disease like ALS and Huntingtons, thats a good place to start.

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Georgia colleges gear up for new semester – AJC.com – Atlanta Journal Constitution

More than 300,000 students return to college and university campuses this month in Georgia.

The biggest changes include a newcampus carry law that allows students with licensed weapons permits to carry firearms on portions of campuses, additional credit to studentswho take approved STEM courses to keep their HOPE scholarships and the repurposing of Turner Field into Georgia States new football stadium.

Heres a look at some changes at some of metro Atlantas largest campuses and the University of Georgia.

The renovation of Rebekah Scott Hall. The $16.5 million project will house a new welcome center, updated offices for admissions and financial aid and residential space for students who will live on the upper two floors.

Atlanta Metropolitan State College

An online Bachelor of Science degree in organizational leadership. It includes a choice of concentration in public service, healthcare administration or office administration and technology.

Its createdthe Department of Cyber-Physical Systems. It will include new bachelor of science programs in cybersecurity, robotics, and data analytics.

The first-two floors of a new $400 million hospital tower opened on July 31, bringing the total number of licensed beds at Emory University Hospital to 733. Patient floors begin opening in late August, and the hospital tower will be fully operational by the end of October.

Awidening of a portion of Clifton Road and its sidewalks, a bike lane, new landscaping and improved visibility of intersections along Clifton Road.

The campus West Village, which includes five micro-restaurants, Panera Bread and Starbucks, music classrooms, and shared meeting rooms.

Georgia Techs West Village, which will include shops, restaurants, classrooms and meeting rooms. PHOTO CONTRIBUTED

The new football stadium, which will have its first game on Aug. 31 against Tennessee State.

A new College of the Arts that offers 20 top undergraduate, graduate and non-degree programs in art, design, music, film, digital media, theater, etc.

New building for its growing Creative Media Industries Initiative.

Kennesaw State University

Students applying to KSU for fall 2018 can choose to apply through a non-binding, early action application or through a regular decision application, a process used by most competitive universities in the state. Meeting the minimum requirements will no longer guarantee a spot at the university.

New degree programs in computer engineering and cybersecurity.

The college is expanding its health science classes. For the first time, classes in human anatomy, microbiology and ethnobotany will be offered this fall to attract more students interested in pursuing careers as dentists, pharmacists, and medical doctors.

Interim president Harold Martin, a former valedictorian. The college is conducting a search process for a permanent president.

The university is breaking ground on the I.W.Ike Cousins for Science and Innovation. The center will have laboratory-classrooms, independent study labs, open study rooms and faculty offices.

The college has a new documentary filmmaking and photography majors beginning this fall. Both new majors are part of the Department of Art & Visual Culture, formerly the Department of Art & Art History.

In September, theyll open a facility to support the Center for Molecular Medicine. The state provided $17 million to support the project. The faculty for this center are working on cures and therapies for diseases such as diabetes, cancer and dementia.

Best quality of life: Emory University (No. 3), Agnes Scott College (No. 20) Great financial aid: Emory University (No. 15) Most conservative students: Berry College (No. 20) Most liberal students: Agnes Scott College (No. 12) Most LGBTQ-friendly: Agnes Scott College (No. 7) Lots of race/class interaction: Agnes Scott College (No. 20) Most beautiful campus: Berry College (No. 9) Most active student government: Agnes Scott College (No. 9) Best college dorms: Emory University (No. 8) Most religious students

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Change in protein production essential to muscle function – Baylor College of Medicine News (press release)

The researchers discovered that the genetic activity of mouse skeletal muscles is particularly intense during the first two weeks after birth; a number of genes alter the amount of proteins produced, while other genes go through alternative splicing and produce different proteins.

Among the genes going through alternative splicing, those involved in calcium-handling functions predominated. Calcium is very important for skeletal and heart muscle because the influx of calcium into the cell stimulates contraction and other functions.

First author Dr. Amy Brinegar, who was a graduate student in the Cooper lab while she was working on this project and recently graduated from the doctoral program in molecular and cellular biology at Baylor, selected three calcineurin A genes, which are involved in calcium-handling functions, and reversed their natural process of alternative splicing in adult mouse muscles. Then, Dr. George Rodney, associate professor of molecular physiology at Baylor, and a graduate student in his lab, James Loehr, who are co-authors on this paper, determined the effect of switching back alternative splicing on functions of isolated adult mouse skeletal muscle in the lab.

They discovered that muscles in which the adult forms of the calcineurin A genes had been switched back to the newborn forms showed a change in calcium flow and were less strong than muscles that retained the adult forms of calcineurin A.

We showed that just by changing three of about 11,000 genes that are estimated to be expressed in adult mouse muscle, we were able to change physiological parameters of those muscles, said Brinegar. This work supports the growing evidence in favor of a physiological role of alternative splicing.

Importantly, about 50 percent of the genes we discovered to undergo alternative splicing are conserved, meaning that the genes go through the same changes both in mice and humans, which opens the possibility of modeling human muscle disorders in the mouse, Cooper said.

Other contributors top this work include Zheng Xia and Wei Li, both from Baylor.

Financial support was provided by National Institutes of Health grants R01AR045653, R01HL045565, R01AR060733, T32 HL007676, R01HG007538, R01CA193466 and R01AR061370. Further support was provided by the Muscular Dystrophy Association grant RG4205.

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Change in protein production essential to muscle function - Baylor College of Medicine News (press release)

MS in Molecular Medicine – Drexel University College of …

The Master of Science in Molecular Medicine (MMED) program provides training in the academic, research and entrepreneurial aspects of the biomedical sciences with an emphasis on translational research in the development of therapeutics and vaccines.

Participation in the program will provide enhanced educational credentials through a flexible curriculum, with most classes offered in the early evening to maximize accessibility. Classes can be attended at two Drexel University College of Medicine locations: Center City and Queen Lane Campuses in Philadelphia. State-of-the-art videoconferencing provides real-time interactive learning at both locations.The program now can also be completed online, with all required courses and many elective courses available.

The Master of Science in Molecular Medicine program is designed to provide academic and practical biotechnological knowledge in translational research, particularly in the areas of molecular therapeutics and vaccine development.

If you prefer an online learning experience, you can still earn a Drexel master's degree in the field of molecular medicine. The online Master of Science in Molecular Medicine program features the same curriculum, flexibility, course content, and instructors as the traditional, face-to-face degree program.

Learn more about the online Master of Science in Molecular Medicine program!

In addition to broad geographic access, the curriculum provides flexibility in content and course load. Most students will complete the program in two years through completion of required courses and electives selected from two menus: research theory and laboratory research. The research experience can be in an academic environment or a company setting, as best fits the individual student's goals and interests.Some students may opt to complete the program on a part-time basis, taking up to four years. In either sequence, no dissertation is required. Program directors and course faculty will work closely with each student to best achieve his or her specific goals.

Learn more about the curriculum

The molecular medicine program is ideally suited for enhancing the scientific credentials of the following groups:

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The Human Heart May Have a Natural ‘Backup Battery’ – Healthline

Researchers say they've found a system in the human heart that allows the organ to restart itself. Their discovery could lead to the replacement of pacemakers.

In an episode of Star Trek: The Next Generation, Lt. Worf is badly injured, but recovers when it is discovered that his body holds a lot of redundant parts and organs for example, 23 ribs that allow him to regenerate.

Science fiction?

Not entirely.

A team of researchers at The Ohio State University Wexner Medical Center discovered that the human heart contains its own fail-safe backup battery system to regulate the heartbeat.

Their findings were published in Science Translational Medicine.

If further testing is successful, fewer people might need mechanical pacemakers in the future.

The potential market is big.

More than 200,000 people in the United States have a pacemaker implanted every year.

The research is still preliminary, but scientists hope to turn it into practical use some day.

In the future we want to develop something that practitioners would welcome, Vadim Fedorov, PhD, an associate professor of physiology and cell biology at The Ohio State University College of Medicine, told Healthline.

Fedorov explained that an implanted pacemaker works by replacing the hearts defective natural pacemaker functions.

The sinoatrial (SA) node, or sinus node, is the heart's natural pacemaker. It's a small mass of specialized cells in the top of the right atrium (upper chamber of the heart). It produces the electrical impulses that cause the heart to beat.

The heart is hardwired to maintain consistency. Irregular heartbeat, or arrhythmia, can be due to heart disease or other problems, such as changes in diet or hormones or electrolyte imbalance.

Optical and molecular mapping of the human heart revealed that the SA node is home to multiple pacemakers, specialized cardiomyocytes that generate electrical heartbeat-inducing impulses.

Total cardiac arrest occurs only when all pacemakers and conduction pathways fail.

Too technical?

Think of it as a car battery. One day your car wont start. Turns out the battery is still good, but one of the connector cables is bad.

So you clean or replace the wire and save yourself from major repairs.

The Ohio State teams discovery showed that the human heart battery restarts itself.

To prove their point, the researchers actually restarted hearts that were destined for the trash heap.

Most of them came from people getting new hearts or accident victims whose hearts were not suitable for transplant.

We kept them in a special solution, he said. When we warm them to body temperature, they will beat.

The discovery, while exciting, is not going to change clinical practice in the next 60 days.

But it offers promise.

Dr. John Hummel, FACC, is a cardiologist at The Ohio State University Wexner Medical Center and is director of the electrophysiology research section and professor of cardiovascular medicine.

He told Healthline the study is intriguing.

These findings finally give us insight as to the actual structure and behavior of the natural pacemaker of the human heart, he said. Diagnosing disease of the natural pacemaker is often straightforward, but can also be one of the more challenging diagnoses to make.

Dr. Fedorovs findings will likely allow us to develop new approaches to discriminate disease from normal behavior of the sinus node, and give our patients a definitive diagnosis of health or disease of the hearts natural pacemaker, Hummel explained.

Funding to translation of this bench research to clinic research is the next step, he added.

Dr. Gordon Tomaselli, professor of medicine, cellular and molecular medicine at the Johns Hopkins School of Medicine and past president of the American Heart Association, expressed similar thoughts.

The work by Vadim Fedorovs group is a beautifully done study on explanted [not used for transplant] human hearts, Tomaselli told Healthline.

He called the infrared optical mapping studies with pharmacological interventions demonstrating the functional redundancy and complexity of the sinoatrial node (SAN) the most compelling part of the work.

Being able to view the hearts in three dimensions increases the researchs usefulness.

Tomaselli pointed out that researchers have known for decades from previous work in animals, and in clinical human electrophysiological labs, that SAN is functionally redundant and anatomically complex.

He urged caution.

I do not think this paper will fundamentally change the management of patients with regard to pacemaker implantation, he said. Although around half of pacemakers are implanted for diseases of the sinus node or atrium, they are implanted not to prolong life but instead to relieve symptoms [fatigue, shortness of breath particularly with exercise].

He went on, The more life-threatening problems with electrical conduction in the heart for which we put in pacemakers to prolong life involve the electrical system that connects the top and bottom chamber [called the AV node] and the conduction system in the lower chambers. This paper does not address this problem.

So, for the meantime, a Klingon skeleton might be your best bet.

See more here:

The Human Heart May Have a Natural 'Backup Battery' - Healthline

Healing turmeric set to woo world – The New Indian Express

Prof Santosh Kumar Kar

BHUBANESWAR:A group of scientists claimed to have developed a medicine from turmeric which is beneficial for many diseases. Produced from nano curcumin, it can be used as anti-cancer, anti-TB and anti-malaria medicine.Lead researcher Prof Santosh Kumar Kar at KIIT University said though the medicine has not been applied on humans, it worked wonder on animals, including rats and dogs.Turmeric (Haldi) has been traditionally used in our food for centuries not only because it spices up our curries but because curcumin, the bioactive polyphenolic compound provides some therapeutic benefits. Researches show that curcumin is not only non-toxic, it can give us relief from pain and help in wound healing, reduce inflammation and tissue damage, he claimed.

As curcumin is very poorly soluble in water and whatever people eat in food goes into blood and shows very little effect, the scientists converted into a bio-available form and developed the nanotised form of pure curcumin to be taken orally for its therapeutic effectiveness.According to the researchers, the nano curcumin showed about five times better bio-availability than the natural curcumin. Its therapeutic efficacy has been tested in mice for various human disease conditions like malaria, cancer and tuberculosis. The bio-available curcumin, when fed to mice infected with the rodent malaria parasite Plasmodium yoelii, the untreated mice died in a few days while the nano curcumin fed mice controlled the infection and survived, Prof Kar said.

Encouraged by the observation, the nano curcumin was tested in a mouse model of breast cancer in collaboration with Prof Gaurisankar Sa of Bose Institute at Kolkata. It was found to modulate T regulatory cell responses and was effective in controlling tumour growth in the mouse.Prof Gobardhan Das of Centre of Molecular Medicine in Jawaharlal Nehru University at New Delhi, who researched on a mouse affected with TB, said the use of nano curcumin in the mouse along with isoniasid not only reduced the time for cure by 50 per cent but the liver at the end of treatment remains intact, the mycobacteria does not show much latency and the immune system of the mice remains intact.

A similar research done under their supervision at the Department of Veterinary Surgery and Radiology, College of Veterinary Science and Animal Husbandry, OUAT by a team, led by Prof Jayakrishna Das, also showed remarkable effect on healing of critical wounds of dogs.Prof Kar said efforts are on to apply it on humans and introduce in the market as a food supplement if not possible as medicine immediately since it involves various administrative works.

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Healing turmeric set to woo world - The New Indian Express

Early cancer-detection method said to find tumors from blood – Press Herald

A recently developed method of diagnosing 13 kinds of cancer from a single drop of blood can lead to early detection of the disease. The relatively inexpensive test puts less burden on patients, but it still needs further improvement in accuracy.

The new blood test was developed by a team of researchers from the National Cancer Center Japan in Tokyo and other entities. They began a clinical test of the method this month. Until now, there has not been a test that could detect so many kinds of cancer at one time.

The test builds hope for treatment at an early stage to reduce cancer deaths, and is also expected to cut down on medical expenses. The team plans to ask the government to put it into practical use as early as within three years.

By using a blood sample taken for a comprehensive medical examination or other checkups, this new test can detect which type of cancer a patient has from an early stage. It is an unprecedented examination method, said Takahiro Ochiya, chief of the Molecular and Cellular Medicine Division at the National Cancer Center Research Institute, who leads the team for the new test.

The researchers focused on a molecular substance called microRNA, or miRNA, as the key to the new technologies. Cancer cells secrete specific kinds of miRNA, which differ depending on the type of cancer.

The team began the research in 2014. After obtaining 8 billion yen of government funds, the team examined secretion patterns of types of miRNA by using blood samples of 40,000 elderly individuals that had been preserved by the institute and other entities. The samples included those from cancer patients as well as people without cancer.

The team successfully detected the patterns of breast, colorectal, pancreatic, biliary tract, esophageal, liver, ovarian, lung, stomach, bladder and prostate cancers, which are major cancers among Japanese people.

They also detected patterns for glioma, which accounts for 30 percent of brain tumors, as well as a rare bone cancer and a type of soft tissue tumor.

The progression of cancer is indicated in four different stages from the early Stage 1 to the most advanced Stage 4.

The researchers were able to diagnose patients with breast cancer including those at Stage 1 by analyzing five types of miRNA, with 97 percent accuracy.

The team also detected other kinds of cancer with at least 95 percent accuracy.

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Early cancer-detection method said to find tumors from blood - Press Herald

Brain-in-a-Dish Models Neuroinflammation – Technology Networks

Credit: Cleber A. Trujillo, UC San Diego

An international team of scientists, led by University of California San Diego School of Medicine researchers, has created a human stem cell-based model of a rare, but devastating, inherited neurological autoimmune condition called Aicardi-Goutieres Syndrome (AGS). In doing so, the team was able to identify unusual and surprising underlying genetic mechanisms that drive AGS and test strategies to inhibit the condition using existing drugs.

Two repurposed FDA-approved drugs showed measurable effect, rescuing cells from the effects of AGS. The findings point to the promise of future clinical trials and to the utility of creating novel stem cell-based models of human diseases when no other models are available.

Our approach can now be used to investigate other neurological conditions, like autism and schizophrenia and overlapping autoimmune disorders that dysfunction in similar ways, said Alysson Muotri, PhD, professor in the UC San Diego School of Medicine departments of Pediatrics and Cellular and Molecular Medicine, director of the UC San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine.

First described in 1984, AGS typically involves early-onset inflammation affecting the brain, immune system and skin. Its severity depends upon which genes are involved there are six types but usually results in pronounced physiological and psychological consequences, from microcephaly (an abnormally small head) and spasticity to skin and vision problems and joint stiffness, all appearing in the first year of life. The syndrome is progressive, resulting in death or a persistent vegetative state in early childhood. Currently, there is no cure; the only treatments are symptomatic or palliative.

The clinical features of AGS mimic those of viral infections acquired in utero, before birth, with increased levels of inflammatory markers and other signatures of inflammatory response. However, Muotri said there is no link between AGS and exogenous pathogens. Previous research has shown that AGS patients have mutations in genes critical to nucleic acid metabolism in the regulation of cellular immune response, among them a deficiency in an enzyme called TREX1, which helps prevent abnormal DNA from accumulating in cells.

Deeper probing into the pathogenesis of AGS has been difficult because animal models do not accurately mimic the human version of the disease. So Muotri, with colleagues, used embryonic stem cells and induced pluripotent stem cells (iPSCs) derived from AGS patients to create six cellular models of the condition. In the past, Muotris lab has developed similar disease-in-a-dish neuronal models of autism, anorexia nervosa and Williams Syndrome, among other rare genetic neurological conditions.

From the iPSCs, they also created cerebral organoids or mini-brains larger clusters of neurons that organize themselves into a cortical structure, similar to a developing human cerebral cortex.

The researchers found that with TREX1 not functioning normally, all of the cell models displayed excess extra-chromosomal DNA and that a major source of the excess DNA came from LINE1 (L1) retroelements. L1s are repetitive sequences of DNA with the ability to autonomously copy-and-paste themselves within the human genome. In the past, they have been called jumping genes and, because their function within cells is largely unknown, junk DNA.

However the term junk DNA is increasingly becoming a misnomer. In work published in 2005, for example, Muotri and colleagues reported that L1s have a high impact on brain cells compared to other tissues, suggesting an important, if so far mysterious, role in brain development.

Since then, he said, researchers around the world have investigated the role of L1s in creating a genetic mosaicism in the brain. These are ancient, genomic parasites that replicate inside our cells. The majority of the current work is focusing on the impact of this genome mosaicism, but we decided to also look outside of the nucleus. And what we found was a big surprise.

In some of the AGS cell models created by the researchers, toxins from excess DNA built up. Others showed an abnormal immune response, secreting toxins that induced cell death in other cells. The combined effect in organoids was a massive reduction in neuron growth when the opposite should occur. These models seemed to mirror the development and progression of AGS in a developing fetus, said Muotri. It was cell death and reduction when neural development should be rising.

The cell death was trigged by the anti-viral response from the L1 molecules outside the nucleus. We uncovered a novel and fundamental mechanism, where chronic response to L1 elements can negatively impact human neurodevelopment, said Charles Thomas, a former graduate student in the Muotri lab and first author of the study. This mechanism seems human-specific. We dont see this in the mouse.

The researchers observed that AGS pathogenesis was similar to a retroviral infection and wondered whether existing HIV antiretroviral drugs might be effective in interfering in L1 replication. Two drugs were tested in the cell models: Stavudine and Lamivudine. Both drugs resulted in reduced L1 and cell toxicity. Cell model growth returned in all cell types and in the complex, differentiated colonies of nerve cells that comprise organoids.

The data supported the idea that HIV drugs could benefit AGS patients, Muotri said. A clinical trial led by study co-author Yanick Crow, MRCP, PhD, at Sorbonne Paris Cite University and the University of Manchester, has already started in Europe.

Muotri said the findings were illuminating and encouraging, providing a platform and impetus for further study of the pathology of neuroinflammation and drug discovery. Its important to note that while this work focused on AGS, nerve cells in schizophrenia show an overabundance of L1 elements and there is an overlap with other autoimmune disorders.

This is a great example of how a fundamental basic research could be rapidly translated into clinics. Are there analogous mechanisms at work in these different diseases? Is this modeling strategy relevant for better understanding and treating them? These are questions we will now pursue.

This article has been republished frommaterialsprovided byUCSD. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Thomas, C. A., Tejwani, L., Trujillo, C. A., Negraes, P. D., Herai, R. H., Mesci, P., . . . Muotri, A. R. (2017). Modeling of TREX1-Dependent Autoimmune Disease using Human Stem Cells Highlights L1 Accumulation as a Source of Neuroinflammation. Cell Stem Cell. doi:10.1016/j.stem.2017.07.009

Link:

Brain-in-a-Dish Models Neuroinflammation - Technology Networks