27.02.2012 - (idw) Max-Planck-Institut f?r Biochemie

Its the small things that matter in life. In structural biology these include proteins, enzymes and viruses. A single change in their molecular structure can mean the difference between function and malfunction, health and disease. On Thursday, February 23, the EU project Instruct launches a new distributed research infrastructure for the science of structural biology. The launch of Instruct will give academic and commercial scientists across Europe access to a full portfolio of integrated technologies. Wolfgang Baumeister, director at the Max Planck Institute of Biochemistry (MPIB) in Martinsried near Munich, Germany, is one of the members of the Instruct consortium. Breakthroughs in biomedical science are a step closer today, with the launch of a new distributed research infrastructure for the science of structural biology. Instruct is the dynamic hub of structural biology providing an integrated infrastructure of cutting edge technology, scientific expertise and pioneering training to enable structure determination from macromolecular to atomic resolution of proteins, protein complexes and single particles. It provides access to some of the most advanced technology in the world and is funded by the European Unions 7th Framework Program. The MPIB contributes as center of European excellence in the field of electron microscopy (EM). It offers state-of-the-art infrastructure for cryo-electron tomography as well as for single particle analysis, the full periphery for sample preparation including ion beam milling and the computational analysis of EM data. A full catalogue of the accessible technology is available on the Instruct Hub at http://www.structuralbiology.eu.

Instruct will be formally launched at a signing ceremony in Brussels on Thursday, February 23, attended by the Principal Investigators of each of the Instruct Centres, the national and regional funding agencies and Robert-Jan Smits, European Commission Director-General for Research and Innovation. Prof. Dave Stuart, Instruct Director, says; Never before have European biologists had a single point of access to all the technology and expertise they need to further their research. By bringing together the different disciplines, technologies and experts in European biology, Instruct will be helping to make the vision of truly integrated biology a reality for the first time.

Contact
Prof. Dr. Wolfgang Baumeister
Molecular Structural Biology
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
E-Mail: baumeist@biochem.mpg.de
http://www.biochem.mpg.de/baumeister

Dr. Julia Rieder
EU Office
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
Phone: +49 (0) 89 8578-2451
E-Mail: rieder@biochem.mpg.de
http://www.biochem.mpg.de/eu jQuery(document).ready(function($) { $("fb_share").attr("share_url") = encodeURIComponent(window.location); });
Weitere Informationen: http://www.structuralbiology.eu/content/instruct-launch-signals-new-opportunitie... - Instruct Press Release http://www.structuralbiology.eu - Instruct Homepage http://www.biochem.mpg.de/en/news/pressroom/index.html - Press Releases of the MPI of Biochemistry

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Unlocking the Secrets of Life Together - New Research Infrastructure for Structural Biology

In order to find a new substance that may one day find its way into a new cancer drug, scientists must first detect suitable drug candidates among all of the possible molecules. Once they have discovered a promising molecule, they must synthesise it and test its effectiveness before its further development into a drug can begin – all in all a laborious and, above all, time-consuming undertaking.

In the early 1990s, researchers pinned their hopes on the assembling of as many molecules as possible with the help of synthesis robots, and then trawling through these vast substance libraries for suitable compounds with the help of automated procedures. However, the initial enthusiasm for this approach soon turned into disillusionment: very few of the newly discovered molecules displayed any effect on living cells, and almost none of them completed the process of development into a finished product.

As a result, Herbert Waldmann and his colleagues at the Max Planck Institute of Molecular Physiology in Dortmund are looking for more efficient methods. The researchers’ main concern here is to both limit the search and simplify the associated synthesis process. “There are simply far too many different compounds to search randomly on the off chance that you’ll stumble onto something,” says Herbert Waldmann. The chemical structural space that includes all possible drug-like structures contains an estimated 1062 different molecules – a number, which, written out in full, fills two thirds of a line on a closely spaced typed page. Therefore, pre-selection is the most important thing.

To this end, the scientists search the chemical structural space using an ingenious computer program called Scaffold Hunter, which was developed at the Max Planck Institute in Dortmund. Scaffold Hunter generates maps of a selected chemical structural space based on structural criteria and enables the researchers to navigate the sea of possible molecules and approach islands of biological activity on the computer screen. “It actually works as simply as a video game,” says Herbert Waldmann. When navigating, the Scaffold Hunter searches for structural motifs that resemble already known structures with a particular biological characteristic. Because chemically related compounds are also very likely to have similar properties, the researchers can track down promising structures in this way. They can then use these as a basis and experiment with different chemical appendages to synthesise new compounds.

But how do the researchers actually know what they should look for? “We take direction from models found in nature,” Herbert Waldmann says, explaining the principle of biology-oriented synthesis (BIOS), based on which the Dortmund scientists carry out their work. “Natural substances were selected over the course of evolution to fulfil important tasks, mostly by binding to a certain protein receptor.” Many of these substances, which arise in animals, plants or microorganisms not only affect their actual target, but also influence human cells. The plant substances morphine and digitalis, which are used for pain relief and in the treatment of heart disease, are a well-known example of this. In total, over one third of all drugs are based on natural substances; in the area of cancer therapy, the proportion is even higher.

Such natural substances and other substances closely related to them are usually complex in structure - the second biggest challenge for the chemists. In order to synthesize the substances, the scientists usually must carry out numerous individual steps in sequence, and repeatedly isolate and purify the intermediate products before they finally obtain the desired end product. Synthesis robots usually fail when faced with the complexity of this task: because they can only master comparatively simple conversions, they can only produce small molecules whose structures are not very complex. Thus, the synthesis of natural substances requires manual work.

However, as Herbert Waldmann and his colleagues have shown, elegant methods are also available for this task. Using a so-called reaction cascade, the team succeeded in synthesising active substances from the centrocountin group – complex molecules with four ring systems in the middle which intervene in cell division and may, therefore, point the way to new anti-tumour drugs. And as is so often the case in science, the discovery arose by chance, as the researchers were actually aiming to synthesise an entirely different molecule. “But the reaction did not unfold as planned and we unexpectedly set a world record,” says Herbert Waldmann. The reaction cascade included a total of twelve steps – a length that has not yet been exceeded in cascade synthesis.

To set the reaction in motion, the researchers simply provided tryptamine and formylchromone and added two catalysts. All of the conversions then proceeded completely automatically, like a domino effect in which all of the tiles fall in succession, once the first one is toppled. The entire synthesis took place in a single vessel and included nine different individual reactions, in which two catalysis mechanisms were involved. “The synthesis of such complex molecules using traditional methods takes days, if not weeks,” says Kamal Kumar, who made a significant contribution to the development of the synthesis method. With the reaction cascade, the production process was successfully completed within a maximum of 30 minutes.

Once the researchers had isolated the new compounds, they wanted to establish, via tests on cell cultures, whether the molecules would have an effect on living cells. They made an important discovery here: following treatment with the centrocountins, during the division phase, instead of two daughter cells, three or more were produced from one cell. However, they were not viable. “The effect is due to the fact that the centrocountins influence the formation of the spindle apparatus,” explains Herbert Waldmann. This spindle-shaped structure usually forms on opposite sides of the dividing cell and ensures that chromosomes are halved and pulled back into the two daughter cells.

As the scientists demonstrated, following the addition of centrocountins, the cells form not two but several attachment points for the spindle apparatus, known as the centrosomes. Because the cell no longer appears to be capable of counting its centrosomes, the researchers gave the substances the name “centrocountins”. Due to the presence of numerous centrosomes, chromosomes are unevenly divided between the daughter cells. The division cycle then comes to a halt and programmed cell death is triggered in the newly produced cells – they commit suicide so to speak.

Could this effect possibly also be used to cause tumour cells to commit suicide? This is the hope of the scientists in Dortmund. The effect of the centrocountins arises from the fact that they bind to two proteins called NPM and Crm1. Both play an important role in the formation of the spindle apparatus and are, therefore, potential target molecules for cancer treatment. “A drug that binds to both NPM and Crm1 has not existed up to now,” says Slava Ziegler, another scientist in Herbert Waldmann’s team.

The researchers do not yet know the precise mechanism by which the newly-discovered substances influence the function of the two proteins. For this reason, they are now focusing on clarifying the biochemical processes involved. When they have obtained this information, they then aim to synthesise a compound based on the centrocountins which cou
ld become a possible active agent candidate – and with a lot of luck, eventually find its way into a new cancer drug.

Provided by Max-Planck-Gesellschaft (news : web)

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Biology-oriented synthesis (BIOS) - cancer drugs based on natural models

FOR many south-west residents, the abundance of seaweed on Warrnambool’s foreshore is little more than an eyesore and a reason to pinch their noses.

But a group of second-year Deakin University marine biology students this week found the slimy mounds to be a habitat rich with life.

In a project designed to improve their ability to sort through marine samples and identify organisms, the students were surprised to find so much activity, according to senior lecturer in marine biology and ecology Alecia Bellgrove.

“It’s a really important component of the ecosystem,” she said.

“A group of second-year marine biology students came back to uni a couple of weeks early for a pre-trimester field trip.

“We wanted to capitalise on the better weather and low tides.

“The main focus is to sample the biodiversity of marine organisms in the local environment.”

Records of the changes in biodiversity over time can also help to explain climate change, Dr Bellgrove said.

The 41 students collected samples of organisms in the seaweed near the harbour pavilion, in the sandstone pools of Lady Bay and in the mouth of Port Fairy’s Moyne River.

“They looked at what sorts of species there are, how many species groups — what’s living where, basically,” Dr Bellgrove said.

“What species are native, what species are occurring naturally and are abundant.

“They’ll get a bunch of different samples and use microscopes to work out what they are in the labs.”

The group scoured the mouth of the Moyne River on Wednesday for organisms living high and low on the shore and under the water.

“Some of them went in a boat ... they were running a dredge along to find out what organisms are living in the sediment on the bottom of the ocean,” Dr Bellgrove said.

The students will work in groups to collate the data for a graded report, the lecturer said.

Next year they will finish the three-year course with a bachelor of environmental science and marine biology.

Yesterday marked the final day of the intensive field trip, which began last Tuesday.

Originally posted here:
Marine biology students seek hidden creatures

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – A group of international research institutes have joined together to launch an initiative to provide access to resources for structural biology research to scientists across Europe and in Israel.

Organized by the European Union's European Strategy Forum of Research Infrastructures program, the Instruct Integrating Biology, or Instruct, initiative will provide academic and commercial researchers access to equipment and expertise spread across 15 collaborating research centers.

The collaborators launched the Instruct initiative at a signing ceremony on Thursday in Brussels, and agreed to provide access to up to 20 percent of their resources.

Instruct will provide access to a range of technologies including tools for proteomic and labeling mass spectrometry applications, computational biology resources, and technologies and expertise for use in sample production, biophysical characterization, crystallization, nuclear magnetic resonance imaging, and others.

"Never before have European biologists had a single point of access to all the technology and expertise they need to further their research. By bringing together the different disciplines, technologies and experts in European biology, Instruct will be helping to make the vision of truly integrated biology a reality for the first time," Instruct Director Dave Stuart said in a statement.

"Instruct will allow laboratories throughout Europe to gain ready access to the most advanced facilities, technologies, and methodologies. Israeli scientists and their European counterparts will now have access to facilities they could only have dreamed of before," added Gideon Schreiber, a professor at the Weizmann Institute and deputy director of Israel's Instruct Core Centre.

The program is based around an online hub that already includes over 500 researchers from 25 countries, and enables them to tailor their online profiles to match their interests and priorities.

Members from institutes in eight countries signed the the agreement joining Instruct on Thursday, including the Czech Republic, France, Germany, Israel, Italy, The Netherlands, Portugal, and the UK.

Original post:
European Institutes Form Structural Biology Resource

By Alison McLennan & Matthew Rimmer

The field of synthetic biology poses a number of challenges for patent law.

With promises of improved medical treatments, greener energy and even artificial life, the field of synthetic biology has captured the public imagination and attracted significant government and commercial investment.

This excitement reached a crescendo on 21 May 2010, when scientists at the J Craig Venter Institute in the United States announced that they had made a “self-replicating synthetic bacterial cell”. This was the first living cell to have an entirely human-made genome, which means that all of the cell’s characteristics were controlled by a DNA sequence designed by scientists.

This achievement in biological engineering was made possible by combining molecular biotechnology, gene synthesis technology and information technology.

Possibilities of synthetic biology
In his autobiography, A Life Decoded, J. Craig Venter contends that synthetic biology has the potential to address concerns about energy security, climate change and sustainable development: “My company, Synthetic Genomics Inc., is already trying to turn an organism into a biofactory that could make clean hydrogen fuel from sunlight and water or soak up more carbon dioxide.”

He elaborated on his long-term scientific aspirations: “From there I want to take us far from shore into unknown waters, to a new phase of evolution, to the day when one DNA-based species can sit down at a computer to design another.”

Venter maintained: “I plan to show that we understand the software of life by creating true artificial life”.

Another leading researcher, Jay D. Keasling, is confident that the field of synthetic biology can increase access to essential medicines – particularly to provide protection against malaria.

However, civil society groups and technology activists have raised concerns about the risks synthetic biology may pose to security, public health and the environment. The ETC Group, for instance, is concerned that organisms made with synthetic biology (such as engineered bacteria) could be released into the environment, with unknown effects. They’re also concerned about potential weaponisation of synthetic biology.

Patentability
There has been much controversy over the application of patent law to emerging technologies, with large legal battles over the patentability of information technology and business methods, genetic testing, medical information, and stem cell research.

The field of synthetic biology also poses a number of challenges for patent law and public policy. One of the most important questions patent experts (such as Professor Graham Dutfield) are asking is whether synthetic biology is too different from previous biotechnologies to apply existing objections to the patenting of living things.

In addition to considering patentability of synthetic biology, patent offices and courts will have to consider the novelty, inventiveness and utility of the claimed inventions and scope of the claims, in light of the scientific knowledge in this field.

In the United States, patent applications for synthetic biology have fallen into two broad categories: ?1) biological tools, methods and products.?
2) computer programs. This includes software for design of biological devices and programs for analysis of biochemical activity within cells.

Some US patent applications have focused on the construction of a synthetic cell. Scientists at the J Craig Venter Institute, for example, have filed applications for patents on a minimal bacterial genome, a synthetic genome and a method of installing a genome into a cell.

Other US patent applications have involved the creation of useful biological products from cells, such as Jay D. Keasling and colleagues’ production of a malaria drug precursor in a genetically modified cell.

There are also patent applications for various methods of biofuel production.

Law reform
US President Barack Obama’s Presidential Commission for the Study of Bioethical Issues recommended that synthetic biology be regulated using the principles of public beneficence, responsible stewardship, intellectual freedom and responsibility, democratic deliberation and justice and fairness.

The Commission was, however, hopeful that synthetic biology could “be developed in an ethically responsible manner”.

But intellectual property expert Arti K. Rai has concerns that, as patent thickets have been a problem in the information technology and biotechnology sector, this could also slow the progress of synthetic biology research.

To counter this risk, some scientists and researchers have called for the introduction of a broad defence of experimental use, under patent law, to protect them from the threat of patent litigation.
The US-based group of scientists, BioBricks Foundation, already promotes open innovation in this field and have created a space to share their own research, right from the establishment of a new field.

Sharing of information and resources in synthetic biology research is facilitated by the Registry of Standard Biological Parts, which is supported by a culture of sharing in the synthetic biology community.

Somewhat more radically, biopunks – do-it-yourself biologists – question the use of intellectual property rights altogether in the field of synthetic biology. The international group of do-it-yourself biologists, known as DIYbio, has groups in North America, Europe and Asia, and individual members in many countries including Australia.

In his book, Biopunk, Marcus Wohlsen explains that in the US he’s observed, “An intellectual property system designed to spur innovation by allowing inventors to profit off their inventions has become in biopunks’ eyes a high-stakes game of low-stakes progress.”

The emerging field of synthetic biology is ripe for law review and reform, both overseas and at home in Australia. We’re seeing a proliferation of patents in this field, with the potential for significant impact on health, the environment and the economy.

If governments are serious about the progress of biological research, they will have to consider the implications of patenting and licensing of synthetic biology.

Alison McLennan ?is a PhD candidate & Vice-Chancellor’s Scholar at the Australian National University, where Matthew Rimmer is an ?ARC Future Fellow and Associate Professor in Intellectual Property. This article was originally published at The Conversation.

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Inventing life: patent law and synthetic biology