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Jon Eisen – Genomic Encyclopedia of Bacteria and Archaea to sample the breadth of microbial diversity

Posted by Dr. Gunn May 28th, 2010 .
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@phylogenomics, @rnaworld, and @comprendia discussing deep scientific matters at the ASM tweetupI recently attended the 2010 American Society for Microbiology General Meeting with my colleague Mary Canady. I’ll be covered the scientific sessions and shared interesting developments in genetics, microbiology, and technology. See also the #ASMGM hashtag on twitter for conference tweets.

Jonathan Eisen spoke Tuesday on the Genomic Encyclopedia of Bacteria and Archaea, an ambitious project to sample across the breadth of microbial diversity and get a sense of just how much genetic diversity is represented across all bacteria. This project was undertaken to get a more balanced picture of genetic diversity, which is currently skewed in modern sequencing projects by under-representation of some groups. Genome sequence data has diverse uses including development of new antibiotics and drugs, as well as for the identification of new species, but without a big picture overview of the “Tree of Life“, scientists are very much like tourists in a strange city without a map, only finding the interesting stuff if they happen to stumble upon it. (more…)

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Stephen Quake Keynote: Single-molecule sequencing shows microbial diversity is greater than expected #ASMGM

Posted by Dr. Gunn May 26th, 2010 .
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I’m blogging this week from the 2010 American Society for Microbiology General Meeting with my colleague Mary Canady. I’ll be covering the scientific sessions and sharing interesting developments in genetics, microbiology, and technology. You can also follow the #ASMGM hashtag on twitter for updates.

Sunday night kicked off the conference with a presentation from Stanford bioengineering professor Dr. Stephen Quake, founder of Helicos Biosciences. Dr. Quake attained a mild amount of fame for being the first person to sequence his own genome, as opposed to the multi-center effort that went into the Human Genome Project.

Dr. Quake’s company Helicos has dramatically reduced the time and cost for sequencing projects, broadly expanding the application reach of sequencing. Faster, cheaper sequencing puts genomes within the grasp of smaller research groups, so it’s no surprise that microbiologists have begun to use it to sequence their favorite subjects.

Because the Helicos instrument is so sensitive, it can actually get a sequence from as little as a single cell, so biologists have begun to sample the “sequence space” of interesting microbiological habitats. One such habitat is the termite gut. Termites have the unique ability to digest wood due to microorganisms resident in their gut, but what Dr. Quake’s collaborators found is that it’s not just one species, but as many as 13 species are present, based on sequences recovered from gut samples. Knowledge of the different species living in this habitat can be used to develop new termite-resistant building materials, but just the fact that 13 different species are found in the gut of this tiny little creature was enough to impress the crowd here. Even more interestingly, it seems that the functions of the microbes are non-overlapping, so it’s no accident all these species are there, rather they serve as a form of evolutionary insurance for the termite. Even though one species would have been enough, having multiple species allows the termite to survive habitat changes that might have been less compatible with the resident bacteria.

As with the sequencing of his own genome, the technical details behind this effort are likewise fascinating (if you ask me, the engineering details nearly put those next to me to sleep). The key advance to make the sequencing work is the applicability of the technique to very small samples, such as you might be forced to work with if you wanted to study a bacteria found in nature that no one has yet learned how to cultivate in the lab. To work with samples in the nanoliter range, they developed an ingenious tiny valve controlled by overlapping expandable microchannels. Inflating one set of tubes would expand the wall into the adjacent tube, shutting of the flow of the adjacent channel. Printing complex patterns via lithography allowed them to sample, mix, and separate volumes small enough to contain a single bacterium. Next, they had to solve the problem of off rates, which are a fundamental limitation to how miniaturized an assay can be. They solved this by using a clear polymer to trap the solution over the assay surface, vastly reducing the volume into which the dye could diffuse.

Speaking before Dr. Quake was Yoshi Kawaoka, describing the synthesis of 1918 flu in the lab, technical advancement that aids the study of modern pandemic flu by comparison with this older, more deadly strain. Further work by Dr. Kawaoka led to the development of a novel neuraminidase inhibitor with activity against pandemic H1N1.

[Disclosures: Dr. Gunn is a San Diego-based scientific consultant and academic community liaison for Mendeley. Former clients include a private single molecule sequencing startup.]

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Flip This Asset: San Diego’s Advanced BioHealing ‘Fixed Up’ Dermagraft for Profit and Growth #BIO2010

Posted by Mary Canady May 5th, 2010 .
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bio_conf-logo1-300x218_2Wednesday I attended a regenerative medicine-focused breakfast at the BIO convention and learned about San Diego company Advanced BioHealing (ABH), who took a ‘fallen’ asset, Dermagraft, and not only turned it into an $85M/year product, but is also looking for new indications. Dermagraft was sold by Advanced Tissue Sciences, who had invested hundreds of millions into developing it, and even got FDA approval for the product to treat diabetic foot ulcers.
I spoke with Advanced BioHealing’s Senior VP Dean Tozer, and he describes their methodology as ‘reverse biotech,’ meaning that they first focused on commercializing products, and just recently hired their CSO Charles Hart. Hart will be spearheading the efforts to find soft tissue indications for Dermagraft. This is counter to how most biotechs in San Diego form, and it appears to be working for ABH as they are predicting 30-50% growth over the next few years.
This growth translates to jobs in San Diego, with 15 listed on the ABH careers page currently. ABH has locations in Westport, Connecticut and Nashville, Tennessee as well, and plans to continue manufacturing products in their 70,000 square foot La Jolla site near the Burnham Institute, and has recently acquired 20,000 square feet of office space nearby in an old Pfizer site. I asked Tozer whether the jobs will continue to be created in San Diego, and he said yes, because the talent pool here is so valuable to them.
What can other San Diego biotechs learn from this example? At BIO this year, I have seen successful repurposing of assets and information. It may simply be the product of a down economy, but I wonder what we can learn, and what could be gained by investigating failed assets that exist from local companies who have not survived? Tozer also believes strongly that the right people make the difference, and they were lucky to bring together a team which understands biotech commercialization. Surely, attracting or training more commercially focused professionals in the area would be a great start.

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How Does Biomarker Stratification Affect Drug Development Cost? It Depends. #BIO2010

Posted by Mary Canady May 5th, 2010 .
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bio_conf-logo1-300x218_2On the San Diego Biotechnology Network LinkedIn group, we asked you what you wanted to hear about from the BIO Convention in Chicago, and you requested to hear about Biomarkers. Tuesday I attended a breakout session titled ‘Impact of Biomarkers on Drug Development Complexity and Cost,’ and it described a study done by panel members Federico Goodsaid of the FDA, Michael Palmer of Adaptive Pharmacogenomics, Mark Trusheim of MIT, Steven Averbuch of BMS, Theresa Long of the Van Andel Institute. The study modeled different scenarios utilizing biomarker information and the financial impact on estimated net present value (eNPV) of developed drugs. The group was truly interdisciplinary, and it was clear from the quality of the presentations that they likely worked well together due to their communication skills.
The session described a workshop held in October of 2009 in which case studies on oncology and alzheimers were discussed (featured in Nature Reviews Drug Discovery as well–requires login).
MIT economist Mark Trusheim began by describing the ‘pharmaeconomics’ of choosing patient populations for clinical trials. There are obvious benefits to using biomarkers to enrich populations, but there are many factors which need to be considered, and ultimately it depends on the science behind the drug and the market. The group determined three factors to be the most important: variability in the therapeutic effectiveness of the drug, prevalence of the biomarker, and the quality of companion diagnostics. Trusheim also described modeling different long term scenarios ranging from Phase II extending through to the end of market exclusivity, from the perfect ‘Nirvana’ situation, where everything goes perfectly, to ‘pharmageddon’ where it goes bad at every turn. Trusheim indicated that in both the oncology and Alzheimer’s study, a very significant increase in eNPV could be achieved by utilizing biomarker information.
Steven Averbuch, VP of Oncology at BMS, covered the study results for Herceptin and Vectibix for oncology indications. In the case of Herceptin, it had a large effect on a small population, saving money and adding to the eNPV by allowing a smaller clinical trial, but perhaps precluding the discovery of other biomarkers or indications for the drug, as was found to be important for drugs such as Gleevec. Vectibix had a large effect on a large population, obviating the need for biomarker stratification but giving the drug a higher eNPV because of a larger market size. Averbuch reiterated Trusheim’s three important factors, and the need for increased communication between all the stakeholders to utilize biomarker information to help move from the ‘pharmageddon’ to nirvana drug development situation.
Theresa Long, presented the study on the Alzheimer’s drug Bapineuzumab, and the effect of biomarker stratification on a chronic condition. They used the ApoE4 biomarker and started with data past Phase 2. Three different scenarios were modeled, from an all-inclusive to stratified, with an 80% increase in eNPV in the biomarker study. Long stressed the importance of knowing the prevalence of the biomarker in the population, even for chronic conditions such as Alzheimer’s which has blockbuster potential.
This session was inspiring as it showed how science can drive drug development and how biomarker stratification could lead pharma and healthcare towards a path of increased communication resulting in lower costs. The study has been submitted for publication and the modeling tools that were used will be available. Federico Goodsaid indicated that the tool could be made available to those who contact him.

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Translational Research Forum at #BIO2010: Learning From the Land of Lincoln

Posted by Mary Canady May 4th, 2010 .
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I attended the translational research forum Monday morning at the BIO 2010 convention in Chicago. The morning started with Congressman Dan Lipinski from Illinois, who was a great choice as he is a member of the House Committee for Science and Technology, as well as the House Committee on Small Business. He is sponsoring the NSF Reauthorization Bill, which will increase the NSF budget to $20B by 2015 and include funding for higher risk/reward projects. The bill will also have provisions for research infrastructure and education. This bill is slated to be brought to the House in the Memorial Day work period, and its passage will of course be beneficial to academic researchers, key to translational research efforts.
Congressman Lipinski also discussed the status of SBIR/STTR reauthorization, which is currently in limbo as there are House and Senate bills which must be reconciled. I did not realize that these programs are currently in a temporary extension and thus vulnerable to be no longer available for small businesses. One of the issues plaguing the reauthorization is the disagreement about whether venture capital (VC) funded companies should be eligible. Lipinski was vague as to the future of this bill, but assured us that these business grants are a high priority, especially since they will help to create jobs in this down economy.
The forum continued with a panel themed ‘From Science to Invention’ containing mostly academic panelists from Illinois, with a representative from Pfizer St. Louis (on the Missouri-Illinois border). Ted Mazzone of University of Illinois Chicago explained the organization of their CTSA (Clinical and Translational Science Awards) center, which has sophisticated infrastructure to support collaboration and commercialization across a ‘mini consortium’ that exists within the CTSAs in Illinois. Stephen Kent from the University of Chicago talked about his experience with translational research from early challenges in vaccine research to studies of the decreasing chiralty of drugs and its affects on NCE approvals. David McCormick from the IIT Research Institute talked about the importance of bioinformatics and stratification of patients.
Dean Welsch, Research Fellow at Pfizer, described his work in the Indications Discovery Unit, where drugs are being repurposed to treat new indications. Efforts to streamline internal information around compounds has been key to making these efforts successful. Pfizer is also looking externally, including a pharma portal within the CTSA to exchange materials or information. He also described how they find new partners and technologies, including utilization of resources such as this web-based network of research centers for Idiopathic Pulmonary Fibrosis. Pfizer also creating a model which they hope will also be adopted more universally called Foci of Expertise, in which CTSA experts can be found and connect. In Welsch’s three years using these methodologies, their modestly sized group has moved 5 compounds into the clinic, which is impressive. Welsch also hinted that a ‘creative’ collaboration between Pfizer and Washington University in St. Louis will be announced soon.
The panel discussed the future of translational research as well. Access to biobanking information, software and informatics challenges, and the traversing the ‘valley of death’ appeared to be the common thread among the discussions. The question that kept nagging me revolves around which entity is ultimately responsible for funding translational research, if any. Government initiatives such as CTSA and NIH Roadmap are certainly important, but are they enough to stimulate the level of collaboration needed? I was encouraged by the level of creativity demonstrated by Pfizer, and I’m guessing this has been driven by the need to economize. Hopefully, lessons that are learned will be applicable more generally. Interesting that I had never heard of a CTSA until today–they seem to be more prevalent in the midwest/east coast, but the Scripps Translational Science Institute is a CTSA. How could we apply these lessons in translational research collaboration in Illinois/Missouri to San Diego biotech?

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