biotechnology

Big pharmas and clinical stem cell research

Attila Csordas — Mon, 29 Sep 2008 10:01:30 -0700

Description

After many years of more or less ignoring the topic, big pharmaceutical companies (revenue in excess of $3 billion) finally are paying attention to stem cells as vehicles of drug testing and future regenerative medicine therapies. The pioneering and highly risky stem cell field has been so far mostly the domain of academic laboratories and small biotech companies.
But these days big pharmas finally started to cooperate with both academia and startups and invest in the range of couple millions of dollars. Some signs of the upcoming trend: GlaxoSmithKline and the Harvard Stem Cell Institute (HSCI) recently (in July, 2008) announced a five-year, $25 million-plus collaborative agreement while Pfizer has already invested $3 million in shares of EyeCyte a La Jolla based early stage stem/progenitor cell-based ophthalmology research and development company.
Stem Cells for Safer Medicines, or SC4SM, a collaboration to develop stem cells for safety testing of new drugs through a public-private partnership and an independent not-for-profit company is backed by 3 European big pharmas, GlaxoSmithKline, AstraZeneca and Roche.
A higher form of involvement means in-house research labs and Pfizer is on that road too with its functional “regenerative medicine unit” in Cambridge, Mass. and with the plans to open another similar shop in the other Cambridge, overseas around this November.
On the drug testing platform stem cell mediated results can be expected much sooner than in the case of an efficient and safe stem cell therapy. According to a 2006 data it takes $1.318 billion and 10-15 years to develop a traditional pharmaceutical drug but no data available on the costs and timeframe of a stem cell based regenerative therapy.

If big pharmas are really risk-taking and invest enough money in stem cell trials in the range of hundreds of million of dollars and if no serious complications occur during the trials then by 2020 or by and large within a decade we can expect some important results from those companies.

But here we should really consider the state of global economy as a big ballast and the tough times in the pharma industry.

What can be expect though with a bigger certainty is that within a decade most of the big pharmas will seriously flirt with stem cells the in the form of setting up in-house research labs, investing in biotech startups and collaborating with the academy.

Sources:

http://www.sc4sm.org/
http://seekingalpha.com/article/79266-pharmaceutical-facts-investors-should-know
http://en.wikipedia.org/wiki/List_of_pharmaceutical_companies

Signals

GlaxoSmithKline collaborates with the Harvard Stem Cell Institute

Pfizer's growing and various interests in stem cells

Regaining vision with gene therapy using adeno-associated viruses

Attila Csordas — Tue, 23 Sep 2008 04:22:28 -0700

Description

Adeno-associated viruses (AAV) are more and more promising candidates as viral vectors for gene therapy. They are small and not pathogenic according to our current knowledge, causing very mild immune response and are able to stably integrate into the host genome's chromosome 19 at a a particular site even in non-dividing cells.

Using viral vectors made out of adeno-associated viruses researchers were able to fully restore the sight of 2 people suffering from Leber's Congenital Amaurosis, an incurable congenital blindness syndrome.

"The RPE65 gene encodes the isomerase of the retinoid cycle, the enzymatic pathway that underlies mammalian vision. Mutations in RPE65 disrupt the retinoid cycle and cause a congenital human blindness known as Leber congenital amaurosis (LCA). We used adeno-associated virus-2-based RPE65 gene replacement therapy to treat three young adults with RPE65-LCA and measured their vision before and up to 90 days after the intervention. All three patients showed a statistically significant increase in visual sensitivity at 30 days after treatment localized to retinal areas that had received the vector. There were no changes in the effect between 30 and 90 days. Both cone- and rod-photoreceptor-based vision could be demonstrated in treated areas. For cones, there were increases of up to 1.7 log units (i.e., 50 fold); and for rods, there were gains of up to 4.8 log units (i.e., 63,000 fold). To assess what fraction of full vision potential was restored by gene therapy, we related the degree of light sensitivity to the level of remaining photoreceptors within the treatment area. We found that the intervention could overcome nearly all of the loss of light sensitivity resulting from the biochemical blockade. However, this reconstituted retinoid cycle was not completely normal. Resensitization kinetics of the newly treated rods were remarkably slow and required 8 h or more for the attainment of full sensitivity, compared with <1 h in normal eyes. Cone-sensitivity recovery time was rapid. These results demonstrate dramatic, albeit imperfect, recovery of rod- and cone-photoreceptor-based vision after RPE65 gene therapy."

Biomedical Sciences and Biotechnology

Source

http://www.pnas.org/content/early/2008/09/19/0807027105.abstract
http://en.wikipedia.org/wiki/Adeno-associated_virus
http://blog.wired.com/wiredscience/2008/09/gene-therapy-bl.html

Senate Committee: water and biotech research to improve health, food security and income generation in Africa and Asia

jorgemata — Fri, 01 Aug 2008 08:33:26 -0700

Description

In page 40 of the report:

Arid Lands.—The Committee recommends USAID consider a proposal to support the International Arid Lands Consortium in addressing water, agricultural, and energy issues in the Middle East and Central Asia.
Dairy Development Programs.—The Committee continues its support for dairy development programs.
Fertilizer Programs.—The Committee recommends consideration of continued support for the International Fertilizer Development Center.
Research.—The Committee recommends up to $30,000,000 for plant and biotechnology research and development programs to improve food security and income generation, particularly in Africa and Asia.
The Committee supports consideration of funding the sustainable food security and global poverty reduction activities of the International Wheat and Maize Improvement Center.
The Committee recommends $29,000,000 for CRSPs. The Committee supports research and development of salt-resistant crops.
The Committee notes the benefits of ridge tillage land use systems in sustainable development in West and Sub-Saharan Africa.
Water.—The Committee recommends not less than $300,000,000 of the funds in this act for programs to implement Public Law 109–121, the Senator Paul Simon Water for the Poor Act of 2005. Of this amount, not less than $125,000,000 should be used in Africa.
The Committee recommends USAID ensure sufficient staff resources for implementing safe water and sanitation programs. The Committee further recommends that up to $20,000,000 be made available to USAID’s Global Development Alliance for public-private partnerships, particularly with NGOs. The Committee notes that the Senator Paul Simon Water for the Poor Act requires the Secretary of State to develop a strategy that elevates the importance of access to safe water and sanitation in U.S. foreign aid programs. The Committee expects the strategy to include numerical goals of people to be provided access to safe water and sanitation.
The Committee notes the work of the International Rural Water Association in providing training and technical assistance to improve the quality of water and health in Central America and the Caribbean.
The Committee recommends USAID consider funding a project in Uganda to increase access to potable water in the Kapchorwa District.
The Committee recommends USAID consider funding proposals for reverse osmosis water purification in developing countries.
The Committee supports the work of USAID to address household water treatment programs, and recommends increased funding to reduce child morbidity and mortality by reducing waterborne illnesses.

Hat tip: AgBioworld.org

Source

Senate Committee: water and biotech research to improve health, food security and income generation in Africa and Asia.
http://appropriations.senate.gov/News/2008_07_21_FY_2009_State,_Foreign_Operations_Report.pdf?CFID=4488692&CFTOKEN=23910981

Is Biotechnology A Victim of Anti-Science Bias in Scientific Journals?

jorgemata — Fri, 01 Aug 2008 08:09:34 -0700

Description

Excerpts:

Primarily outside the scientific community, misapprehensions and misinformation about recombinant DNA- modified (also known as 'genetically modified', or 'GM') plants have generated significant 'pseudo-controversy' over their safety that has resulted in unscientific and excessive regulation (with attendant inflated development costs) and disappointing progress. But pseudo controversy and sensational claims have originated within the scientific community as well, and even scholarly journals' treatment of the subject has been at times unscientific, one-sided and irresponsible. These shortcomings have helped to perpetuate 'The Big Lie' - that recombinant DNA technology applied to agriculture and food production is unproven, unsafe, untested, unregulated and unwanted. Those misconceptions, in turn, have given rise to unwarranted opposition and tortuous, distorted public policy.

Introduction

The production of pharmaceuticals with recombinant DNA technology [also known as gene-splicing or genetic modification] has enjoyed significant successes over a quarter century, with minimal controversy. However, the use of recombinant DNA-modified plants for food, feed and environmental applications has not fared as well. Primarily outside the scientific community, misapprehensions and misinformation have generated significant 'pseudo-controversy' over the plants' safety. The ensuing misconceptions have resulted in excessive, unscientific regulation, inflated development costs and disappointing progress. But pseudo controversy and sensational, inaccurate claims by activists have appeared within the scientific community as well, and even scholarly journals' treatment of the subject - especially the aspects related to environmental or health risks - has been at times unscientific, one-sided and irresponsible. Examples of the failure of editorial judgment and/or peer review abound, including the appearance of flawed, misleading articles in Nature, The Lancet, Science and Proceedings of the National Academy of Sciences USA (PNAS) that never should have been published.

Inconsistencies in editorial policies

Often, these shortcomings reflect internal inconsistencies. For example, in 1992 Nature editorialized: 'The same physical and biological laws govern the response of organisms modified by modern molecular and cellular methods and those produced by classical methods . [Therefore] no conceptual distinction exists between genetic modification of plants and microorganisms by classical methods or by molecular techniques that modify DNA and transfer genes' [1]. These conclusions seem clear and unequivocal (as well as obvious) enough, but more recently Nature has rejected or neglected such sentiments in both editorials and the reporting of 'news'. Their news correspondents sometimes seem to be ignorant of context and to rely extensively on unreliable, biased sources; and the supervising editors apparently are unwilling or unable to correct them. Repeatedly, Nature has offered undue credibility and coverage to doctrinaire critics and skeptics of recombinant DNA technology. A recent example occurred in a September 2007 news article, 'Biotech crop rules get rewrite' [2]. This description of a U.S. Department of Agriculture (USDA) initiative to revise the regulation of recombinant DNA-modified organisms was exceedingly one-sided and misleading. The article cited the concerns of 'critics' who believe that the changes in regulation 'will not go far enough to protect the environment and public health', whereas an examination of the comments in the official docket (USDA dossier #APHIS-2006-0112) suggests that a fairer and more accurate rendering would be: 'many prominent academic experts fear that the changes will not make the existing flawed regulatory approach more scientifically defensible and risk-based.'

As numerous academics pointed out in their comments in the official docket, the existing USDA regulatory approach - the basic tenet of which is that the use of the most precise and predictable techniques (viz, recombinant DNA) elicits a discriminatory and excessive regulatory regime - violates the principle of proportionality (which holds that the degree of regulatory scrutiny should be commensurate with the degree of risk posed by a product or activity); under the USDA's oversight, the amount of scrutiny applied to field trials and commercialization of new plant varieties is actually inversely related to risk. Paradoxically, recombinant DNA-modified organisms, the most precisely crafted and most predictable organisms - that is, those generally posing the least risk - are the most regulated. Excessive regulation has markedly inflated the costs of performing field trials; a field trial with a recombinant DNA-modified plant costs 10-20 times as much as one with a phenotypically identical plant modified with conventional techniques [3].

The approach to regulation taken by the USDA conflicts not only with scientific consensus and common sense but also with official overarching statements by the U.S. government about the principles that should guide regulatory policy, which are congruent with the viewpoint of the 1992 Nature editorial quoted above. In turn, this viewpoint reflects an authoritative 1989 analysis of genetic modification technologies by the United States National Research Council that summarized the contemporary scientific consensus: 'With classical techniques of gene transfer, a variable number of genes can be transferred, the number depending on the mechanism of transfer; but predicting the precise number or the traits that have been transferred is difficult, and we cannot always predict the phenotypic expression that will result. With organisms modified by molecular methods, we are in a better, if not perfect, position to predict the phenotypic expression' [4]. Nature's correspondent in the September 2007 article ignored this essential context completely. We will not speculate whether Nature's slanted characterization of the responses to the USDA's proposal was a rookie correspondent's mistake or whether it represents the insensitivity of the journal's editors to the importance of science as the basis for public policy.

The worst case: publication of flawed research The publication of shoddy or misleading news articles pales beside the appearance of flawed research articles - for example, the 2001 paper by Quist and Chapela in Nature that ostensibly demonstrated gene flow from maize that contains genetic material from Bacillus thuringiensis (Bt-maize) into native landraces of maize in Oaxaca, Mexico [5]. These supposedly positive results were based on dubious methodology, as colleagues had pointed out to the authors months before submission to Nature. The publication of the article triggered scientific criticism from major research groups that was published subsequently in Nature [6,7], and eventually the original article was condemned by the editor in chief: 'In light of these discussions and the diverse advice received, Nature has concluded that the evidence available is not sufficient to justify the publication of the original paper' [8].

However, although both reviewers and editors rejected additional evidence submitted subsequently by the original authors to support their original conclusions, Nature published the new 'evidence' [9] in order 'to allow our readers to judge the science for themselves' [8]. This seems to be an abdication of the usual formal process of peer review, the purpose of which is to subject experimental data to expert vetting prior to publication. Philip Campbell, the editor of Nature, avers that, 'The independence of our editorial decision-making from partisan anti- or pro-technology agendas and from commercial interests is paramount in our role as a journal' [10]. Perhaps he should add 'competence and professional behaviour of editors and reviewers' to what Nature considers to be 'paramount'.

It is noteworthy that later examination of 150 000 maize samples in Oaxaca found no trace of Bt genes [11], and no other group has confirmed the results of Quist and Chapela. Ironically, however, even if the original report by Quist and Chapela had been correct, the finding of gene flow would have been inconsequential. As botanist Peter Raven observed, 'Whether or not transgenes are present in landraces in Oaxaca at present, they will inevitably be found in them as time passes, because of the nature of the indigenous agriculture.' He added, 'There they will persist if they confer a selective advantage on the plants in which they occur, or they may disappear if they do not confer such an advantage in the prevailing conditions. Such genes are no more 'invaders' into the populations concerned than any other genes' [12].

Nature is not alone in exhibiting an apparent bias against biotechnology. In 2000, Science published a 'research article' by L.L. Wolfenbarger and P.R. Phifer that was both trivial and obviously flawed [13].

[...]

Editorial negligence or a failure of the peer review process?

Equally as shocking as the publication of such a shoddy paper in a major journal was the lack of an appropriate response from Professor Randy Schekman, the editor of PNAS, to numerous complaints about it (including from members of the Academy), some of them quite detailed. After promising to discuss the paper during the regular conference of the journal's associate editors, he appears to have decided to ignore the problem in the hope that it would go away. The only concession from PNAS was to agree to publish online a 250-word letter to the editor - along with a rebuttal of the same length from the original authors! We would remind Professor Schekman that in science, as in politics, the cover-up is often as bad as - or worse than - the original transgression.

These kinds of failures of quality control and - though we flinch at having to say it - the integrity of journals' correspondents, editors and peer reviewers inflict irreparable harm on the traditional process by which new scientific knowledge is obtained and reported. They corrupt the reporting and archiving of scientific developments for the scientific community, the popular press and the public, and they exert a broad ripple effect: within weeks of the flawed PNAS article being published, it was cited by European Union environmental regulators as the justification for the imposition of a ban on the sale of recombinant DNA-modified seeds [19].

Bias and negligence in the peer-review process are not, of course, limited to articles related to recombinant DNA technology. In May 2007 the journal Cancer, a publication of the American Cancer Society (ACS), ran a special online supplement that concluded that breast cancer is caused by trace chemicals in the environment, including pesticides, chemicals in cosmetics and substances such as PCBs and DDT [20]. As observed by Dr Elizabeth Whelan, president of the New York-based American Council on Science and Health, the paper contained several obvious, severe flaws and should not have survived peer review [21]. In addition, she pointed out the damage caused by the popular press's uncritical acceptance of the findings and that the journal and the ACS performed a grave disservice to the public. Instead of bolstering the notion that what Dr Whelan characterised as 'allegedly inescapable, invisible, hostile chemical agents' are a major cause of cancer, they should have reminded women to take prudent precautionary measures, such as regular mammograms and vaccination against human papilloma virus [21].

Ensuring the integrity of peer review

Because science is (or is supposed to be) self-correcting - a thesis is put forth, tested and ultimately revised on the basis of new data - corruption in the form of misinformation conveyed to the scientific community distorts the entire process. As Dr Whelan has pointed out (personal communication to H.I.M.), 'the peer review process is all we have in terms of quality control on what gets published. We should therefore fiercely protect the integrity of peer review. This means that the editors of these journals have the responsibility to choose the highest quality, unbiased peer reviewers - and to be alert to inherent biases.' When the editor of a preeminent scientific journal (who requested anonymity) was queried about the examples cited in this paper, he offered a similar suggestion: 'When a manuscript arrives that offers evidence bearing on a topic of intense political controversy - and the issue of risks associated with organisms modified using recombinant DNA is surely one - reviewers should be chosen who either have no recorded position on or involvement in the controversy, or who provide representation of both sides (in which case a third reviewer may have to be selected eventually!).'

More specifically, we suggest that journals should encourage their referees to ask probing, detailed questions and that the authors of the submitted article should be required to answer them to the satisfaction of the reviewers before a paper is accepted.

Had these sorts of measures been taken in the case of the research articles described above, it is unlikely that any of them would have been published in a prominent journal. But what if editors lack the courage or integrity - or simply the time - to undertake these measures? Will the scientific community take them to the woodshed? Only time will tell.

Source

Is Biotechnology A Victim of Anti-Science Bias in Scientific Journals? Miller, H., Morandini, P., & Ammann, K (2008), Trends in Biotechnology, Electronic Prepublication Febr. 17, March, 2008, pp 122-125; doi:10.1016/j.tibtech.2007.11.011. http://www.botanischergarten.ch/Peer-Review/Miller-Morandini-Ammann-Peer-Review-2008.pdf

Bacteria make major evolutionary shift in the lab - life - 09 June 2008 - New Scientist

Max Marmer — Thu, 12 Jun 2008 11:50:37 -0700

Description

A major evolutionary innovation has unfurled right in front of researchers' eyes. It's the first time evolution has been caught in the act of making such a rare and complex new trait.

sometime around the 31,500th generation, something dramatic happened in just one of the populations - the bacteria suddenly acquired the ability to metabolise citrate, a second nutrient in their culture medium that E. coli normally cannot use.

Indeed, the inability to use citrate is one of the traits by which bacteriologists distinguish E. coli from other species. The citrate-using mutants increased in population size and diversity.

"It's the most profound change we have seen during the experiment. This was clearly something quite different for them, and it's outside what was normally considered the bounds of E. coli as a species, which makes it especially interesting," says Lenski.

In the meantime, the experiment stands as proof that evolution does not always lead to the best possible outcome. Instead, a chance event can sometimes open evolutionary doors for one population that remain forever closed to other populations with different histories.

Biomedical Sciences and Biotechnology

Source

http://www.newscientist.com/article/dn14094-bacteria-make-major-evolutionary-shift-in-the-lab.html

DNA Computer Puts Microbes to Work as Number Crunchers: Scientific American

Max Marmer — Wed, 11 Jun 2008 13:33:26 -0700

Description

It's not your normal, electronic silicon-based machine, but scientists have made a computer from a small, circular piece of DNA, then inserted it into a living bacterial cell and unleashed the microbe to solve a mathematical sorting problem.

"A computer is any system that can read some input and give some readable output," says Karmella Haynes, a biologist at Davidson College in North Carolina and co-author of a new study appearing in the Journal of Biological Engineering. Haynes and her team looked to harness the power of DNA recombination to solve the so-called "burnt pancake problem": a puzzle about how to stack different-size flapjacks that are burned on one side and perfectly cooked on the other using the fewest number of flips to arrange them so the largest are on the bottom and all are golden side up.

"DNA computers may be able to accomplish things that electronic computers cannot," says Len Adleman, a molecular scientist at the University of Southern California. "For example, it is very hard to conceive putting an electronic, silicon-based computer into a bacterial cell."

The promise of DNA computers in cells lives in the opportunity for parallel processing: Because cells are alive and replicate, copying the plasmid segments and the Salmonella enzyme into new cells, the number of individual processors working on a problem continuously multiplies, potentially allowing them to reach a solution faster than electronic silicon-based computers, Haynes explains.

Biomedical Sciences and Biotechnology

Source

http://www.sciam.com/article.cfm?id=dna-computer-puts-microbe

Acceleration in innovation global sourcing and in emergence of locations of research capacity and advanced technical skills

jorgemata — Wed, 07 May 2008 02:57:24 -0700

Description

From newly published "Innovation in Global Industries,", by the Board on Science, Technology, and Economic Policy, a boards that advises the National Academies:

The debate over offshoring of production, transfer of technological capabilities, and potential loss of U.S. competitiveness is a long-running one. Prevailing thinking is that the world is flat that is, innovative capacity is spreading uniformly; as new centers of manufacturing emerge, research and development and new product development follow.

Innovation in Global Industries challenges this thinking. The book, a collection of individually authored studies, examines in detail structural changes in the innovation process in 10 service as well as manufacturing industries: personal computers; semiconductors; flat-panel displays; software; lighting; biotechnology; pharmaceuticals; financial services; logistics; and venture capital. There is no doubt that overall there has been an acceleration in global sourcing of innovation and an emergence of new locations of research capacity and advanced technical skills, but the patterns are highly variable. Many industries and some firms in nearly all industries retain leading-edge capacity in the United States. However, the book concludes that is no reason for complacency about the future outlook. Innovation deserves more emphasis in firm performance measures and more sustained support in public policy....

Table of Contents:

Front Matter i-xiv
Introduction--Jeffrey T. Macher and David C. Mowery 1-18
1 Personal Computing--Jason Dedrick and Kenneth L. Kraemer 19-52
2 Software--Ashish Arora, Chris Forman, and JiWoong Yoon 53-100
3 Semiconductors--Jeffrey T. Macher, David C. Mowery, and Alberto Di Minin 101-140
4 Flat Panel Displays--Jeffrey A. Hart 141-162
5 Lighting--Susan W. Sanderson, Kenneth L. Simons, Judith L. Walls, and Yin-Yi Lai, 163-206
6 Pharmaceuticals--Iain M. Cockburn 207-230
7 Biotechnology--Raine Hermans, Alicia Löffler, and Scott Stern 231-272
8 Logistics--Anuradha Nagarajan and Chelsea C. White III 273-312
9 Venture Capital--Martin Kenney, Martin Haemmig, and W. Richard Goe 313-340
10 Financial Services--Ravi Aron 341-372

East and Southeast Asia: Science and Technology

Source

Innovation in Global Industries. Board on Science, Technology, and Economic Policy (STEP). http://books.nap.edu/catalog.php?record_id=12112

Human proteome project

Attila Csordas — Tue, 06 May 2008 21:33:18 -0700

Description

Finally a complete ‘Human Proteome Project’ is in the pipeline. It aims the tissue-level complete knowledge of the human proteome revealing “which proteins are present in each tissue, where in the cell each of those proteins is located and which other proteins each is interacting with”. Keep in mind also that around 21′000 human genes encode 1 million different proteins and that the effort cannot localize exactly which cell types in a given tissue is producing which protein. According to Nature’s Helen Pearson: Biologists initiate plan to map human proteome

“Those involved in the draft plan say that a human proteome project is now feasible partly because estimates of the number of protein-coding genes have shrunk. It was once thought that there might be around 50,000 or 100,000, but now, just 21,000 or so are thought to exist, making the scale of human proteomics more manageable. And the group plans to focus on only a single protein produced from each gene, rather than its many forms.

The plan is to tackle this with three different experimental approaches. One would use mass spectrometry to identify proteins and their quantities in tissue samples; another would generate antibodies to each protein and use these to show its location in tissues and cells; and the third would systematically identify, for each protein, which others it interacts with in protein complexes. The project would also involve a massive bioinformatics effort to ensure that the data could be pooled and accessed, and the production of shared reagents.”

The idea is to analyze and list all the proteins manufactured by chromosome 21 within 3 years as a pilot study and then finish the whole project within 10 years. Chromosome 21 is the smallest child in the family and likely contains between 200 and 400 genes, so the pilot study can yield us a couple hundreds proteins. Another powerful idea is to start with the human mitochondrial proteome which is around 1000-1500 proteins as far as I know, that is at least 3 times as many as encoded by chromosome 21.

“Steven Carr, director of proteomics at the Broad Institute in Cambridge, Massachusetts, says there is likely to be broad support for a large-scale proteomics effort, but much debate about how best to do it. Rather than analyse the proteome of one chromosome, he says it may be better to tackle the proteome of mitochondria or the cell membrane because it would reveal more about biology and diseases related to those structures. “It’s time to think about something in a systematic fashion — whether this is the project is a different question,” he says.”

Source:

Helen Pearson: Biologists initiate plan to map human proteome Published online 23 April 2008 | Nature | doi:10.1038/452920a http://www.nature.com/news/2008/080423/full/452920a.html
Human proteome project: 21000 genes/1 protein, 10 years, $1 billion? http://pimm.wordpress.com/2008/04/23/human-proteome-project-21000-genes1-protein-10-years-1-billion/#more-1462

Signals

Human Liver Proteome Project

Human Plasma Proteome Project

Attila Csordas — Tue, 06 May 2008 21:24:39 -0700

Description

The Human Plasma Proteome Project (PPP) is organized under The Human Proteome Organisation (HUPO) and considered to be a sister project of The Human Liver Proteome Project (HLPP).

The long term goals of this project are:
* Comprehensive analysis of plasma and serum protein constituents in people
* Identification of biological sources of variation within individuals over time, with validation of biomarkers
o Physiological: age, sex/menstrual cycle, exercise
o Pathological: selected diseases/special cohorts
o Pharmacological: common medications
* Determination of the extent of variation across populations and within populations

What has been reached so far:

"During 2003-2005, the PPP prepared and distributed reference specimens of human serum and plasma to 55 participating laboratories worldwide, stimulated access to emerging technologies, and generated substantial datasets and integrated databases for proteins detectable and identifiable in human serum and plasma. Experimental protocols used combinations of depletion, fractionation, mass spectrometry, and immunoassay methods linked via search engines and annotation groups to gene and protein databases. We created a new human plasma proteome database and have developed recommendations for use in future studies with plasma and serum.

Collaborating laboratories and working groups of the PPP Pilot Phase addressed (a) specimen stability and protein concentrations; (b)protein identifications from 18 MS/MS datasets, including subproteome analyses; (c) independent analyses from raw MS/MS spectra; (d) search engine performance; (e) biological annotations and insights; (f) antibody arrays; and (g) direct MS/SELDI analyses. MS/MS datasets had 15710 different International Protein Index (IPI) protein IDs; the PPP integration algorithm applied to multiple matches of peptides sequences yielded 9504 IPI proteins identified with one or more peptides and 3020 proteins identified based on two or more peptides (the Core Dataset). These proteins have been characterized with Gene Ontology, InterPro, Novartis Atlas, Online Mendelian Inheritance in Man, and immunoassay-based concentration determinations. The database permits examination of many other subsets, such as 1274 proteins identified with three or more peptides. Reverse protein to DNA matching identified proteins for 118 previously unidentified ORFs.

The findings from the collaborative project and from lab-specific ancillary projects are published in a special issue of Proteomics, "Exploring the Human Plasma Proteome", August 2005, which was presented to all registrants at the HUPO 4th World Congress on Proteomics in Munich."

Biomedical Sciences and Biotechnology

Source

HPPP overview http://www.hupo.org/research/hppp/
Proteomics THE HUPO Human Plasma Proteome Project http://www3.interscience.wiley.com/journal/114292023/abstract?CRETRY=1&SRETRY=0

Human Liver Proteome Project

Attila Csordas — Tue, 06 May 2008 21:04:56 -0700

Description

The proteome is the sum of all the proteins produced by an organism/tissue/cell population in a given timeframe. According to the ExPASy Proteomics Server: "Proteomics can be defined as the qualitative and quantitative comparison of proteomes under different conditions to further unravel biological processes."
The Human Proteome Organisation (HUPO) is an international scientific organization representing and promoting proteomics through international cooperation and collaborations by fostering the development of new technologies, techniques and training.

The Human Liver Proteome Project (HLPP) is a big ongoing and pilot project of HUPO:

"The overall aim of this project is to: generate an integrative approach that will lead to a comprehensive functional map of the liver; expand the liver proteome to its "PHYSIOME" and "PATHOME" in order to accelerate the development of liver-specific diagnostics and therapeutics; and develop standard operating procedures (SOPs) that will be applied to this and all other HUPO Initiatives.

The SOPs for collection, preparation and distribution of liver samples were established. Using the established SOPs, Prof. He and collaborators accepted samples from collaborators in both France and China and expression profiling was performed. In all, 4975 unique proteins and 2338 groups with 9245 proteins involved were identified from the French liver tissue samples. The transcriptome of human liver tissue, with 15426 genes, has been established and analyzed, in which 11806 are known genes and 3620 are EST. The bank for the ORFs has been established and there are more than 2700 full-length ORFs collected. A crude PPI network has been drafted, with 1291 proteins involved where the value is higher than 90. In addition, a murine hybridoma cell bank against human liver and plasma proteins, using unknown and native proteins as the immunogens, has been established. Among them, more than 1000 monoclonal antibodies reacted specifically with the 100 most highly abundant proteins in human liver and plasma. Meanwhile, in June 2005, at the HLPP workshop organized by Dr. Beretta, a subproject focused on Hepatocellular Carcinoma (HCC) was launched."

Biomedical Sciences and Biotechnology

Source

ExPASy Proteomics Server http://expasy.org/proteomics_def.html
Human Proteome Organisation http://www.hupo.org/
Human Liver Proteome Project - HLPP http://www.hupo.org/research/hlpp/

Implantable medical devices may expose patients to security risks

csimard — Wed, 30 Apr 2008 15:43:24 -0700

Description

A team of researchers from three leading universities has demonstrated that patients' private medical information could be extracted and their devices reprogrammed without the patients' authorization or knowledge.

"We hope our research is a wake-up call for the industry," said Kohno, an assistant professor of computer science and engineering at the University of Washington. "In the 1970s, the Bionic Woman was a dream, but modern technology is making it a reality. People will have sophisticated computers with wireless capabilities in their bodies. Our goal is to make sure those devices are secure, private, safe and effective."

Source

University of Washington (2008, March 17). Implantable Medical Devices May Expose Patients To Security, Privacy Risks. ScienceDaily. Retrieved April 30, 2008, from http://www.sciencedaily.com /releases/2008/03/080312134128.htm

Nanotope: Regenerative Medicine Company in IL

Matt Daniels — Fri, 18 Apr 2008 09:25:00 -0700

Description

"Nanotope is a regenerative medicine company that leverages a core set of proprietary technologies to address multiple therapeutic markets. This highly flexible and customizable platform was first developed at Northwestern University by Dr. Samuel I. Stupp, Professor of Materials Science & Engineering, Chemistry and Medicine and Director of the Institute for BioNanotechnology in Medicine (IBNAM). Nanotope is developing a suite of products, each customized to regenerate specific tissues; including neuronal, vascular, bone, myocardial, and cartilage. The products are injectable compounds that work with surviving cells in and around the point of damage to initiate and support tissue regeneration and growth. Once regeneration is complete, the compounds are safely broken down and removed by the body. Nanotope’s lead products target neuron regeneration for prevention or reversal of paralysis associated with spinal cord injury and angiogenesis for advanced wound healing and the treatment of peripheral artery disease."

The Technology:

Nanotope is building a suite of products to be injected into injured tissue, or in the case of wound healing, to be applied topically. Upon injection, the products form a substrate that actively directs surviving cells to re-grow damaged tissue. The technical basis underlying this is a customizable chemical matrix, or gel, of nanofibers that provides three-dimensional bioactive scaffolding in which cells and tissues may grow and differentiate. Two primary features of the gel are its customizable bioactivity and controlled gelation. These features result from engineered small individual molecules that self-assemble into nanofibers under physiological conditions. This proprietary technology was developed by Dr. Samuel Stupp at Northwestern University.

The molecules forming the gel have two distinct regions: a hydrophilic head region that confers bioactivity to the gel and a hydrophobic tail. The molecules are entirely customizable to control everything from the rate of self-assembling to the type of bioactivity conferred by the fully-formed gel of nanofibers. The bioactive head region is a short peptide sequence derived from a protein or peptide that exerts an influence of interest on target tissues. The number of different bioactive regions is limitless and may be engineered to elicit specific cell responses. It is this factor that allows Nanotope to use the same core technology for regeneration of different types of tissues.

This technology provides a flexible and broad platform of “smart” materials to elicit tissue regeneration and healing across diverse cell types when it would otherwise not occur.

Future of chemistry

Source

http://www.nanotope.com/index.php

U of Minnesota researchers discover key for converting waste to electricity

Alex Soojung-Kim Pang — Sun, 02 Mar 2008 21:00:00 -0800

NOTE: This content was aggregated from RSS feed. Original source is http://www.eurekalert.org/pub_releases/2008-03/uom-uom030308.php

EurekAlert reports on new research on bioelectric bacteria-- bacteria that produce electricity.

Researchers at the University of Minnesota studying bacteria capable of generating electricity have discovered that riboflavin (commonly known as vitamin B-2) is responsible for much of the energy produced by these organisms.

The bacteria, Shewanella, are commonly found in water and soil and are of interest because they can convert simple organic compounds (such as lactic acid) into electricity, according to Daniel Bond and Jeffrey Gralnick, of the University of Minnesota’s BioTechnology Institute and department of microbiology, who led the research effort.

“This is very exciting because it solves a fundamental biological puzzle,” Bond said. “Scientists have known for years that Shewanella produce electricity. Now we know how they do it.”

The discovery means Shewanella can produce more power simply by increased riboflavin levels....

Scaled-up “microbial fuel cells” using similar bacteria could generate enough electricity to clean up wastewater or power remote sensors on the ocean floor.

“Bacteria could help pay the bills for a wastewater treatment plant,” Bond said.

But more ambitious applications, such as electricity for transportation, homes or businesses, will require significant advances in biology and in the cost-effectiveness of fuel cell materials.

Reprogramming differentiated cells offers alternative to embryonic stem cells

Attila Csordas — Thu, 22 Nov 2007 08:47:03 -0800

Description

Stem cells are able to renew themselves and could differentiate into other type of cells. Regenerative medicine is the science and technology built around stem cells’ regenerative capacity. Successful reprogramming of differentiated human somatic cells into a pluripotent, embryonic stem (ES) cell-like state would allow creation of patient- and disease-specific stem cells instead of using controversial embryonic stem cells. The generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors was reported (1).

American (2) and Japanese (3) researchers recently demonstrated that the same technique (but with different set of 4 genes) can turn human cultured skin cells into induced pluripotent stem (iPS) cells that meet the defining criteria for human ES cells and are similar to ES cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. These cells could differentiate into cell types of the three germ layers in vitro and in vivo in teratomas. The significant exception is that iPS cell are not derived from the embryo nor were made by the therapeutical cloning technique in in which the nucleus of a differentiated cell is placed in an oocyte that is then activated to divide to form an embryo.

What are the future implications of these findings?

Similar to human ES cells, human iPS cells should prove useful for studying the development and function of human tissues.
Disease and patient specific cells: the reprogrammed induced pluripotent cells could be made from patients with known diseases. If the root causes of disease were genetic that could be a better way to study disease, say genetically matched cells from patients would enable them to study complex diseases, like Alzheimer’s, in the laboratory.
Discovering and testing new drugs: Human iPS cells should make it easier to generate panels of cell lines that more closely reflect the genetic diversity of a population, and should make it possible to generate cell lines from individuals predisposed to specific diseases.
For transplantation therapies based on these cells, with the exception of autoimmune diseases, patient-specific iPS cell lines should largely eliminate the concern of immune rejection.
If it works, the technique -- technically known as somatic cell dedifferentiation -- promises to solve the two great downfalls involved in producing embryonic stem cells: the controversial destruction of embryos and reliance on a limited supply of eggs.
The new method includes potentially risky steps, like introducing a cancer gene with engineered viruse. But stem cell researchers say they are confident that it will not take long to perfect the method and that today’s drawbacks will prove to be temporary. It is important to understand, however, that before the cells can be used in the clinic, additional work is required to avoid vectors that integrate into the genome, potentially introducing mutations at the insertion site.
The method is a direct rival of the other reprogramming technique called terapeuthical cloning based on somatic cell nuclear transfer.
The reprogrammed skin cells may yet prove to have subtle differences from embryonic stem cells that come directly from human embryos, and further work is needed to determine if human iPS cells differ in clinically significant ways from ES cells.

Peer-review literature:
1. K. Takahashi, S. Yamanaka, Cell 126, 663 (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126:663-76

2. Takahashi et al. (2007) Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined
Factors Cell (2007), doi:10.1016/j.cell.2007.11.019 PDF

3. Yu et al. (2007) Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells Science, Published online 20 November 2007; 10.1126/science.1151526

Media coverage:
Nature Reports Stem Cell: Human reprogramming changes everything, and nothing

Wired Science: Skin Cell-to-Stem Cell Alchemy 'Like Turning Lead Into Gold'

New York Times: Scientists Bypass Need for Embryo to Get Stem Cell

Signals

Therapeutic and Research Uses of RNA Interference

Alex Soojung-Kim Pang — Tue, 23 Oct 2007 11:10:30 -0700

Description

New discoveries by cell biologists regarding the role of RNA in gene regulation have provided researchers with a powerful tool that will likely have wide-ranging impact. These discoveries have also spurred the formation of biotechnology companies aiming to develop RNA-based therapies.

"Research on RNA, the intermediary messenger molecule between DNA and protein synthesis, has long been of secondary interest compared to DNA. Discoveries in the last decade, however, have shown RNA to have a complex role in gene regulation. An especially significant discovery is that some kinds of RNA can interfere with gene expression after translation from DNA. This phenomenon of RNA interference causing 'gene silencing' is leading to a fundamental revision of the understanding of the role of RNA. In the next decade, researchers will continue to sort out the function of RNA. The research is likely to have a significant impact on models of the cell and theories about genetic regulation and inheritance, specifically by challenging the notion of the exclusive power of DNA. Researchers hypothesize that the newly discovered property of what is now called small interfering RNA (siRNA) may be to protect the cell from viruses and provide a way of achieving genomic stability. The molecule may also play a role in development, perhaps offering a way to better understand stem cells. Of perhaps even greater consequence is that scientists have already learned to harness this natural genetic machinery to experimentally 'silence' the expression of specific genes.

The implications of this biological tool for new therapeutic strategies, as well as new genetically modified organisms, are being explored by the biotechnology industry with intense interest. Some new biotechnology companies have formed primarily around the concept of developing RNA-based therapies. Notwithstanding the industry investments, some critics believe that effective clinical applications of this new discovery may be decades away at best and point to past clinical disappointments with antisense RNA therapies, which were meant to treat genetic disorders by deactivating messenger RNA from a particular gene. Furthermore, the potential therapeutic benefits are likely to be costly and difficult to administer, suggesting wealthy countries and individuals stand to benefit the most initially."

This will be enabled by:

Dissemination of research protocols to expand the use of RNA interference as a research tool
Investment from biotechnology companies to expand the range of potential clinical applications

Early indicators include:

The journal Science's naming of the discovery of RNA interference as 'breakthrough of the year' in 2002
Acuity Pharmaceutical's filing with the US Food and Drug Administration in August 2004 of a new investigational drug application involving the therapeutic use of RNA interference

What to watch:

Commercial 'gene silencing' kits for research become available.
Results of long-term clinical trials show the efficacy of RNA-based therapies for age-related macular degeneration.
A Nobel Prize is awarded for research on the mechanics of RNA interference and downgrading of DNA as the 'master molecule'.

Signals

Nanowire Sensors for DNA Testing

Alex Soojung-Kim Pang — Tue, 23 Oct 2007 11:10:30 -0700

Description

Testing of DNA with nanowire sensors is likely to replace traditional DNA tests, making such testing less expensive, faster, and more widely available as a diagnostic tool.

Highly sensitive sensors that employ nanomaterial science could enable the optoelectronic and electrochemical detection of DNA. Such sensors could allow single-drop-sized samples of DNA, from blood, urine, or saliva, to be tested for viral DNA, a genetic disorder, or drug interactions. Inexpensive and fast tests based on these sensors could allow earlier disease detection and provide a way of genotyping patients that is lower cost than the microarrays currently used. The early lead that microarrays have in research however could become an advantage when genotyping moves into the clinical setting.

Aside from their use in DNA testing, electronic sensors based on nanoscience, unlike chemical tests, would be operationally convenient to use in field settings, and potentially capable of detecting a wide range of materials with clinical, defense, and environmental relevance.

At present, it is not clear which of the competing technologies for nanowire sensors (for example, lithography and self-assembly) will be most successful."

This will be enabled by:

Increased production and lowered cost of carbon nanotubes

Early indicators include:

Demonstration by Harvard University researchers that it is possible in real time to detect sequences of DNA that cause cystic fibrosis by using a sensor made from nanowires
Design by researchers at Hewlett Packard of a 50-nm silicon-based sensor employing lithographic patterning techniques for the sequence-specific detection of DNA in very small quantities

What to watch:

Manufacture of nanowire sensors based on one technology or another proves itself by resulting in rapidly falling cost per unit.
Genotyping moves into the clinical setting and nanowire sensors predominate over microarrays there due to their lower cost.