Newswise DALLAS Aug. 7, 2020 UT Southwestern scientists have developed a genetically engineered mouse and imaging system that lets them visualize fluctuations in the circadian clocks of cell types in mice. The method, described online in the journal Neuron, gives new insight into which brain cells are important in maintaining the bodys master circadian clock. But they say the approach will also be broadly useful for answering questions about the daily rhythms of cells throughout the body.
This is a really important technical resource for advancing the study of circadian rhythms, says study leader Joseph Takahashi, Ph.D., chair of the department of neuroscience at UT Southwestern Medical Center, a member of UT Southwesterns Peter ODonnell Jr. Brain Institute, and an investigator with the Howard Hughes Medical Institute (HHMI). You can use these mice for many different applications.
Nearly every cell in humans and mice has an internal circadian clock that fluctuates on a roughly 24-hour cycle. These cells help dictate not only hunger and sleep cycles, but biological functions such as immunity and metabolism. Defects in the circadian clock have been linked to diseases including cancer, diabetes, and Alzheimers, as well as sleep disorders. Scientists have long known that a small part of the brain called the suprachiasmatic nucleus (SCN) integrates information from the eyes about environmental light and dark cycles with the bodys master clock. In turn, the SCN helps keep the rest of the cells in the body in sync with each other.
What makes the SCN a very special kind of clock is that its both robust and flexible, says Takahashi. Its a very strong pacemaker that doesnt lose track of time, but at the same time can shift to adapt to seasons, changing day lengths, or travel between time zones.
To study the circadian clock in both the SCN and the rest of the body, Takahashis research group previously developed a mouse that had a bioluminescent version of PER2 one of the key circadian proteins whose levels fluctuate over the course of a day. By watching the bioluminescence levels wax and wane, the researchers could see how PER2 cycled throughout the animals bodies during the day. But the protein is present in nearly every part of the body, sometimes making it difficult to distinguish the difference in circadian cycles between different cell types mixed together in the same tissue.
If you observe a brain slice, for instance, almost every single cell has a PER2 signal, so you cant really distinguish where any particular PER2 signal is coming from, says Takahashi.
In the new work, the scientists overcame this problem by turning to a new bioluminescence system that changed color from red to green only in cells that expressed a particular gene known as Cre. Then, the researchers could engineer mice so that Cre, which is not naturally found in mouse cells, was only present in one cell type at a time.
To test the utility of the approach, Takahashi and his colleagues studied two types of cells that make up the brains SCN arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) cells. In the past, scientists have hypothesized that VIP neurons hold the key to keeping the rest of the SCN synchronized.
When the research team looked at VIP neurons expressing Cre in just those cells, so that PER2 luminesced green in VIP cells, while red elsewhere they found that removing circadian genes from the neurons had little overall effect on the circadian rhythms of the VIP neurons, or the rest of the SCN. Even when VIP neurons no longer had a functioning clock, the rest of the SCN behaved essentially the same, explains Yongli Shan, Ph.D., a UTSW research scientist and lead author of the study. Nearby cells were able to signal to the VIP neurons to keep them in sync with the rest of the SCN, he says.
When they repeated the same experiment on AVP neurons, however removing key clock genes not only did AVP neurons themselves show disrupted rhythms, but the entire SCN stopped synchronously cycling on its usual 24-hour rhythm.
What this showed us was that the clock in AVP neurons is really essential for the synchrony of the whole SCN network, says Shan. Thats a surprising result and somewhat counterintuitive, so we hope it leads to more work on AVP neurons going forward.
Takahashi says other researchers who study circadian rhythms have already requested the mouse line from his lab to study the daily cycles of other cells. The mice might allow scientists to hone in on the differences in circadian rhythms between cell types within a single organ, or how tumor cells cycle differently than healthy cells, he says.
In all sorts of complex or diseased tissues, this can let you see which cells have rhythms and how they might be similar or different from the rhythms of other cell types.
Takahashi holds the Loyd B. Sands Distinguished Chair in Neuroscience.
Other UTSW researchers who contributed to this study were Yan Li, Mariko Izumo, Kimberly Cox, Byeongha Jeong, and Seung-Hee Yoo, who is now at UT Health Science Center in Houston. Collaborators were John Abel and Francis Doyle of Harvard Medical School and David Olson of the University of Michigan.
This research was supported by funds from the HHMI, the National Institutes of Health (R01 NS106657, R01 GM114424, T32-HLO9701, F32-AG064886), and The Welch Foundation (AU-1971-20180324).
About UTSouthwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 24 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.
- Reducing barriers to mainstream gene therapy - BioPharma-Reporter.com - September 4th, 2020
- Mapping Genetic Diversity of Lung Tumors Over Time May Lead to More Effective Therapies - UCSF News Services - September 4th, 2020
- Multi-site study to evaluate the role of testing guidelines in ensuring access to genetic information for men with prostate cancer - PRNewswire - September 4th, 2020
- Global Prime Editing Market to Witness Heightened Growth During the Period 2020 2030 - The Daily Chronicle - September 4th, 2020
- Liquid biopsies to disrupt the oncology testing market - Medical Device Network - September 4th, 2020
- Global RNA-interference (RNAi) Market Growth, Trends and Forecasts to 2025: Focus on Key Players Alnylam Pharmaceuticals, Arrowhead, Quark... - September 4th, 2020
- Yale researchers find a cause and possible treatment for Fragile X - Yale News - September 4th, 2020
- 'Coming into their own': FDA approval of liquid biopsy tests puts early, less invasive cancer detection in broader reach - USA TODAY - September 4th, 2020
- Fusion Genes Associated With More Aggressive Papillary Thyroid Cancer in Pediatric Patients - Targeted Oncology - September 4th, 2020
- Existing Class of Drugs May Improve Neurological Function in Patients with Rare, Aggressive Genetic Disorder - Newswise - September 4th, 2020
- Genomic analysis reveals insights on virulent, emerging foodborne pathogen - UB Now: News and views for UB faculty and staff - University at Buffalo... - September 4th, 2020
- Hyperthyroidism is associated with breast cancer risk and mammographic and genetic risk predictors - 2 Minute Medicine - September 4th, 2020
- Health history platform launches to trace genetic conditions | Digital Healthcare - Healthcare Global - Healthcare News, Magazine and Website - September 4th, 2020
- New HIV Gene Therapy, CAR-T Treatments Could be on the Horizon for Patients - BioSpace - September 4th, 2020
- Cell Suicide Gene Further Linked to Immunotherapy Response - Technology Networks - September 2nd, 2020
- Genetic mutations may be linked to infertility, early menopause - Washington University School of Medicine in St. Louis - September 2nd, 2020
- How to use precision medicine to personalise COVID-19 treatment according to the patient's genes - Down To Earth Magazine - September 2nd, 2020
- UCT professors research offers hope of treatment for sickle cell anaemia - Daily Maverick - September 2nd, 2020
- Association of recent stressful life events with mental and physical health in the context of genomic and exposomic liability for schizophrenia - 2... - September 2nd, 2020
- Finding order in the chaos of cancer mutations - Drug Target Review - September 2nd, 2020
- Mustang Bio Announces Orphan Drug Designation for MB-107 for the Treatment of X-linked Severe Combined Immunodeficiency in Newly Diagnosed Infants -... - September 2nd, 2020
- Novavax Announces Publication of Phase 1 Data for COVID-19 Vaccine Candidate in The New England Journal of Medicine - GlobeNewswire - September 2nd, 2020
- Department of Genetic Medicine | Johns Hopkins Medicine - August 10th, 2020
- Genetic Medicine | Internal Medicine | Michigan Medicine ... - August 10th, 2020
- Genetic Medicine | Department of Medicine - August 10th, 2020
- Genomics and Medicine - Genome.gov - August 10th, 2020
- New Approach to Treating Osteoarthritis Advances | NYU Langone News - NYU Langone Health - August 10th, 2020
- Stoke Therapeutics Reports Second Quarter Financial Results and Provides Business Updates - Business Wire - August 10th, 2020
- Here's Why Shares of Editas Medicine and Beam Therapeutics Are Soaring Today - Motley Fool - August 10th, 2020
- Grant will fund study into COVID outcome disparities in NYC - Cornell Chronicle - August 10th, 2020
- A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate - Science Advances - August 10th, 2020
- Spark Therapeutics Deepens Drug Development Expertise in Hematology and Rare Disease with Appointment of Gallia G. Levy, MD, Ph.D., as Chief Medical... - August 10th, 2020
- Chromosomal Rearrangements Associated with Chemotherapeutic Drug Resistance | McDonnell Boehnen Hulbert & Berghoff LLP - JD Supra - August 10th, 2020
- Jae Jung, Ph.D., Appointed as Chair of Cleveland Clinic Lerner Research Institute's Department of Cancer Biology - Health Essentials from Cleveland... - August 10th, 2020
- The UK and TCELS to jointly support COVID-19 research in Thailand - GOV.UK - August 10th, 2020
- Akouos Announces Expansion of Executive Team and Board of Directors - BioSpace - August 10th, 2020
- Medical and neurobehavioural phenotypes in male and female carriers of Xp22.31 duplications in the UK Biobank. - Physician's Weekly - August 10th, 2020
- Coronavirus vaccine breakthrough: New generation cure that stops virus developed - Express - August 10th, 2020
- Global Cell and Gene Therapy Market, Forecast to 2025 by Product, Disease, End-user and Region - COVID-19 Updated - PRNewswire - August 10th, 2020
- Not Everyone Needs 8 Hours of Sleep, New Research Reveals | Time - TIME - August 10th, 2020
- Lindsey Criswell Named Director of National Institute of Arthritis and Musculoskeletal and Skin Diseases - UCSF News Services - August 10th, 2020
- Kazia Therapeutics hits A$1 on grant of Rare Pediatric Disease Designation to paxalisib for DIPG - Proactive Investors USA & Canada - August 10th, 2020
- Treatment Considerations for Prostate Cancer Progressing After Combination Therapy for mCSPC - UroToday - August 10th, 2020
- Edited Transcript of PSNL.OQ earnings conference call or presentation 6-Aug-20 9:00pm GMT - Yahoo Finance - August 10th, 2020
- Ovid and Angelini partner on treating Angelman syndrome in Europe - Pharmaceutical Technology - August 10th, 2020
- Doctoral Student/Research Assistant in Mitochondrial Biology and Signalling job with UNIVERSITY OF HELSINKI | 218596 - Times Higher Education (THE) - August 10th, 2020
- Simpler COVID-19 test could provide results in hours from saliva - University of Wisconsin-Madison - August 10th, 2020
- This company has a better version of a simpler, faster Covid-19 test - STAT - August 7th, 2020
- Mental Notes: Music Cognition Lab is dedicated to the scientific study of how music affects the brain and behavior - Vanderbilt University News - August 6th, 2020
- Nasha Fitter Elected to Board of Directors of the ACMG Foundation for Genetic and Genomic Medicine - PRNewswire - August 5th, 2020
- HDAC6 Can Control Tumor Growth and Halt Metastasis in Triple-Negative Breast Cancer - Newswise - August 5th, 2020
- Will programming a cell ever be as easy as programming an app? - SynBioBeta - August 5th, 2020
- Penn Researchers Identify New Genetic Cause of a Form of Inherited Neuropathy - Newswise - August 5th, 2020
- Genetic Variant in Persons of African Descent Linked with Stroke: Analysis - DocWire News - August 5th, 2020
- Invitae Reports $46.2 Million in Revenue Driven by More Than 120000 Samples Accessioned in the Second Quarter of 2020 - Monterey County Weekly - August 5th, 2020
- Noel R. Rose, widely regarded as the father of autoimmune disease research, dies at 92 - The Hub at Johns Hopkins - August 5th, 2020
- Atsena Therapeutics acquires exclusive rights to Gene Therapy for GUCY2D-associated Leber Congenital Amaurosis - GlobeNewswire - August 5th, 2020
- Seragon Announces GenomeScore, the First AI Platform to Measure Rate of Aging and Physiological Changes - PRNewswire - August 5th, 2020
- Vaccine 'durability': COVID-19 immunizations coming soon but will they last? - Genetic Literacy Project - August 5th, 2020
- Aerpio Pharmaceuticals, Inc. Announces a Second Clinical Trial with Funding from MTEC to Evaluate Razuprotafib for the Prevention and Treatment of... - August 5th, 2020
- Stoke Therapeutics to Present at Upcoming Investor Conferences in August - Business Wire - August 4th, 2020
- The global cell and gene therapy market by revenue is expected to grow at a CAGR of over 30.90% during the period 20192025 - GlobeNewswire - August 4th, 2020
- Cochlear implant uses LEDs to tackle hearing loss - Optics.org - August 4th, 2020
- Rozlytrek, Roche's first tumour-agnostic therapy, approved in Europe for people with NTRK fusion-positive solid tumours and for people with... - August 4th, 2020
- Alnylam Pharmaceuticals : Submits CTA Application for ALN-HSD, an Investigational RNAi Therapeutic for the Treatment of Nonalcoholic Steatohepatitis -... - August 4th, 2020
- 'The younger the child, the likelier to find causative gene of infant epilepsy' - Korea Biomedical Review - Korea Biomedical Review - August 3rd, 2020
- Known genes associated with male infertility doubled - BioNews - August 3rd, 2020
- Alnylam Submits CTA Application for ALN-HSD, an Investigational RNAi Therapeutic for the Treatment of Nonalcoholic Steatohepatitis (NASH) - Business... - August 3rd, 2020
- Cancer drug is first therapy to emerge from 23andMe-GSK deal - STAT - STAT - August 3rd, 2020
- Dr. Rana on the Rationale for Video Genetic Counseling in Prostate Cancer - OncLive - August 3rd, 2020
- Metastatic Lung Cancer Study Finds That Bionano's Saphyr Outperforms NGS for the Detection of Structural Variants - GlobeNewswire - August 3rd, 2020
- Health Media in the COVID-19 Era: A mid-wave report - Features - MM&M - Medical Marketing and Media - August 3rd, 2020
- Cyberpunk 2077 shows off the ruined dreams district of Pacifica in new concept art - Critical Hit - August 2nd, 2020
- An unsupported American conspiracy theory found a foothold in Europe. New research shows how - NewsDio - August 2nd, 2020
- Study Suggests New Approach to Improve Radiation Therapy Resistance in Glioblastoma - Michigan Medicine - August 1st, 2020
- Atsena Therapeutics acquires exclusive rights to Gene Therapy for GUCY2D-associated Leber Congenital Amaurosis - BioSpace - August 1st, 2020
- Our Genes May Explain Severity of COVID-19 and Other Infections - Quanta Magazine - August 1st, 2020
- Omega Therapeutics Lands $85M to Tap Into Control Room of Biology - Xconomy - August 1st, 2020
- EarlyBird Study: Early Detection of Adult-Onset Type 2 Diabetes in Youth - Diabetes In Control - August 1st, 2020
- Movers & Shakers, July 24 | BioSpace - BioSpace - July 31st, 2020