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Biotechnology, Health and Business in Canada, the United States and Worldwide

Tag Archives: stem cells

Friday Science Review: May 28, 2010

A Map to Better Beer? The key signaling protein-protein interactions in yeast have been mapped.  Mass spectrometry was used to discover the global network between protein kinases and phosphatases to generate the “kinome” map, which contains 1844 interactions.  Since yeasts are model organisms with similar signaling pathways as in human cells, this information is relevant for human disease research and drug design.  The data set in this study was so large that the research team created software to store and analyze the data (ProHits) and perform statistical analysis (SAINT).  Dr. Mike Tyers (Samuel Luenefeld Research Institute) is the lead author of the project described in Science magazine.  The entire data set is available at the yeastkinome.org resource website.

Shhhh… Improving Gene Silencing: Micro RNAs (miRNA) control gene expression by interfering with specific RNA transcripts and this requires the Argonaute proteins (AGOs) to perform this function.  Researchers isolated the specific key region in AGO and solved the crystal structure of this segment.  From this, they discovered that there are intricate and specific molecular interactions between the miRNA and AGO that can dictate specificity.  As RNA interference techniques are gaining traction in the therapeutic arena, this discovery may lead to modifications to enhance the effectiveness of these therapies.  Dr. Bhushan Nagar led the McGill University research team and published the findings in Nature or check out this video podcast.

E. coli Survival Switch: The AceK protein in some bacteria acts as a switch responding to stressful environmental cues, allowing the bacteria to bypass the energy-producing Krebs cycle and go into a conservation mode.  Bacteria such as E. coli and Salmonella can survive in low-nutrient environments such as water.  Therefore, the discovery of how AceK works provides a potential target to prevent bacterial contamination in drinking water by inhibiting the ability of the bacteria to go into survival mode.  Dr. Zongchao Jia and postdoctoral fellow Dr. Jimin Zheng at Queen’s University solved the structure of the protein that led to understanding the unique properties of the enzyme in having both phosphorylation and de-phosphorylation activities on the same protein.  This breakthrough is described in the latest edition of Nature.

Little Buggers All Over Us: The Human Microbiome Jumpstart Reference Strains Consortium is trying to catalog all the microbes in the human body.  We are covered by millions and millions of these little critters – as many as 10x more microbes than the number of cells in our body, but they’re not necessarily bad for us.  They actually play important roles in protecting against infection, aid with digestion, developing our immune system and keeping us healthy.  So far, 178 genomes have been sequenced with the goal to sequence around 900 genomes.  The NIH initiated the project and Dr. Michael Surette and his team at the University of Calgary is a major contributor to the study.  The first phase of this initiative is published in Science.

Genomic Modifications in Stem Cells: To further understand stem cells and embryonic development, scientists took a closer look at how the structural organization of genomic DNA (chromatin and histones) plays a role in determining what tissue they become.  They identified and compared specific modifications across the genome that either activates or represses gene expression in different stem cells.  The value of this information is that it suggests differential regulatory mechanisms controlling development and depends on the specific stem cell lineage.  The safety of regenerative medicine lies in these types of studies in basic stem cell biology.  Developmental biologist Dr. Janet Rossant at The Hospital for Sick Children led the study, which appears in the Proceedings of the National Academy of Sciences.  Also, congratulations to Dr. Rossant as a recent recipient of the 2010 Premier’s Summit Award for Medical Research.

Improving Alzheimer Immunotherapy: Delivering antibodies against amyloid-beta peptide (Abeta) directly into the brain is more effective than systemic delivery in reducing amyloid plaques, as demonstrated in a mouse model.  In this novel approach, transcranial focused ultrasound (FUS) was applied to improve permeability of the blood brain barrier without the need for high doses of the antibody.  The researchers administered the therapeutic antibody intravenously along with a contrast agent to follow the progress via MRI imaging.  Using this MRI guided FUS method, they could see the contrast agent enter the brain within minutes and amyloid pathology was improved in the mouse model after four days.  Drs. Kullervo Hynynen and Isabelle Aubert at Sunnybrook Research Institute published their study on-line in PLoS One.

X-Prize Ventures Further Into Biology: Millions May Be Up for Grabs for New Organs from Stem Cells and New Doctors from Software

A story in FierceBiotech reports that the X Prize Foundation, most famous for incentivizing Burt Rutan’s SpaceShipOne, is considering a “stem cell” prize that would award $10 million to

“the first team to be able to create a lung, liver, or heart from the stem cell of a patient who is terminal, have that new organ transplanted into the patient and have them live for a year.”

This is not the Foundation’s first venture into biology.  The Archon X Prize for Genomics — still likely out of reach of current technology — will also award $10 million for

“the first Team that can build a device and use it to sequence 100 human genomes within 10 days or less… at a recurring cost of no more than $10,000 per genome.”

Nor will the stem cell prize be the last biology X Prize.  In the CNet interview noted by FierceBiotech, Foundation Chairman and CEO Peter Diamandis is enthusiastic about an “an artificial intelligence physician,” that can equal or best the diagnostic skills of a panel of 10 doctors.

Prizes are a valid alternative to patents as a method of incentivizing innovation, are widely used in IT, and have a long history of successes beginning with navigation in the 1700’s and food canning in the 1800’s. 

Although prizes seem to risk market distortion and intentionally duplicative efforts, the goals set out by the X Prize foundation — full-genome sequencing, new organs from our own cells, and accurate automated diagnoses — are as much the stuff of dreams as commercial space travel and cars that drive themselves.  These big dreams create beneficial externalities, like publicity for the ideas and fame for the winners, that encourage more students to take up similar challenges.

Friday Science Review: February 12, 2010

New Discovery for Neonatal Diabetes: Researchers uncovered an important role for the Rfx6 gene.  Its integrity is required for normal development of the islets of Langerhans cells in the pancreas that produces important hormones including insulin.  Genetic mutations found in Rfx6 are the cause of severe neonatal diabetes where there are no insulin producing islets of Langerhans cells.  To prove the critical role of Rfx6 in directing the differentiation of early pancreatic cells, researchers disrupted the gene in mice and observed the development of an identical disorder as displayed in humans.   Identifying the gene is a key piece of the puzzle and will lead to new avenues to find treatments for all types of diabetes.  Dr. Constantin Polychronakos and his team at McGill University collaborated with researchers from UCSF and report their study in the on-line edition of Nature.

Controlling Stem Cell Fate: A genome-wide screen identified the PCL2 (polycomb-like 2) gene as a key decision maker in determining the fate of stem cells.  This is an important area of research because stem cell based therapies in regenerative medicine are on the rise but more thorough understanding of stem cell control is necessary for safety reasons.  In the absence of PCL2, stem cells can no longer differentiate into specialized cells regardless of adding stimulating factors to try to push it to differentiate.  Once they re-introduced PCL2 into the stem cells, they were able to drive differentiation again.  By mapping the network of genes that PCL2 regulates, they can trace the steps in the path of a stem cell in becoming one of the many cell types in our body.  University of Toronto scientist, Dr. William Stanford and his team describe their research in the journal Cell Stem Cell.

Stem Cell Prediction: This is a neat study.  Researchers generated an algorithm to predict the future of a stem cell – whether it divides and self-renew as stem cells or produce alternate cell types.  They recorded video of retinal progenitor cells under the microscope to ‘observe’ the cell’s characteristic dynamic behaviour and movements just prior to dividing.  This information was computed to generate a predictive algorithm that was tested to be (amazingly!) 99% accurate in identifying cells that will self-renew as stem cells and 87% correct in predicting a differentiation cell fate.  This may lead to new tools to help scientists isolate pure populations of stem cells for their future studies.  Dr. Michel Cayouette’s group at the Institut de Recherches Cliniques de Montréal presents their work in this week’s edition of Nature Methods.

Genomics of Flesh-eating Disease: The genomic sequences of Streptococcus bacterial strains from past epidemics in Ontario were determined in a study involving Canadian and US researchers.  They identified and compared single nucleotide polymorphisms (SNPs) between the strains and found that they were different by an average of only 49 SNPs.  Each strain, however, also contained unique sequences that could be used for tracking purposes in future outbreaks.  Some genes were highly variable, which is information that they can use to try to understand the bacterial virulence factors at play in gaining an advantage over the infected person.  These comparative pathogenomic studies are invaluable for microbial epidemiology research and for shedding light on new potential targets for antibiotic drugs.  Drs. Donald Low and Allison McGeer at Mount Sinai Hospital participated in the research that is reported in this week’s edition of the Proceedings of The National Academy of Sciences.

Friday Science Review: October 30, 2009

Regenerative medicine and Cross-border awards…

Gene Therapy Saves Donor Lungs: A technique using gene therapy on donor lungs before transplantation may be used to repair and save damaged lungs, making them potentially suitable for transplantation into patients.  The procedure involves first preserving the lungs at normal body temperature in a protective chamber called the Toronto XVIVO Lung Perfusion System, which continuously pumps a solution of oxygen, proteins and nutrients.  Next, adenovirus gene therapy is used to introduce the IL-10 cytokine gene into the lungs.  IL-10 helps to decrease inflammation, which would lead to improved health and function of the donor lungs and better outcome for the patient.

Dr. Shaf Keshavjee, the project leader at the McEwen Centre for Regenerative Medicine, describes the rationale:

“It’s as if gene therapy turbocharges each individual cell to manufacture many more proteins in its own IL-10 factory.”

“This protein down-regulates or decreases the inflammatory potential of cells injured before and during the transplant process. It also has the capacity to turn down the recipient’s immune system which rejects the transplanted organ.”

The research study is reported in this week’s issue of Science, Translational Medicine.

A Platform to Test Cardiac Cell Therapy:  A model system for evaluating stem cell transplant in cardiac cell therapy to repair damaged heart tissue is described in this study by Drs. Peter Zandstra and Milica Radisic’s team at the University of Toronto.  Using their engineered heart tissue (EHT) as the analytical platform, they applied stem-cell derived cardiac cells and measured molecular and electrophysiological parameters of the EHT.  The system was verified as a predictive strategy to interrogate different cell transplantation conditions for the capacity to survive and functionally integrate into heart tissue.  This tool should help researchers accelerate development of cardiac cell therapy strategies and it can also provide mechanistic insight into the challenges of a successful transplant.  On a personalized medicine theme, an advantage of the system is that the EHTs are customizable and can be derived from individuals for patient specific testing prior to the actual treatment.  The study appears in this week’s edition of the Proceedings of the National Academy of Sciences.

“Cross-border” Cancer Stem Cell Therapy Award: The Collaborative Partnership Program between the California Institute for Regenerative Medicine (CIRM) and the Cancer Stem Cell Consortium (CSCC) in Canada have awarded two internationally recognized Canadian researchers with support to lead their respective cancer stem cell based therapy projects.

One project will develop agents to directly target leukemic stem cells that are resistant to current therapies.  This will be co-led by Dr. John Dick, Princess Margaret Hospital and Dr. Dennis Carson, University of California San Diego.

The other project will develop small molecules targeting cancer-initiating cells within solid tumor cancers and will be co-led by Dr. Tak Mak, Princess Margaret Hospital and Dr. Dennis Slamon, University of California, Los Angeles.

The awards offer each project up to $40 million (USD) over four years, with funding for the Canadian investigators contributed by Genome Canada and Canadian Institutes of Health Research through the CSCC and funding for the Californian investigators contributed by CIRM.

Congratulations to Drs. John Dick and Tak Mak!

Top 10The Scientist magazine ranked Dalhousie University in Halifax and the University of Toronto in the top 10 best places to work in academia outside of the U.S. Based on a web survey of scientists regarding job satisfaction, pay, research resources and relationships with their peers and management, Dalhousie ranked 5th and U of T came in at 10th place.  It is very nice to see Canadian institutions and our great research environment recognized by peers around the world.

BIO 2009: Ontario Premier’s Breakfast

BIO 2009The speeches (s-peach-es?) just finished this morning at the Ontario Premier’s breakfast.

Minister of Research and Innovation John Wilkinson announced that Ontario has recently completed 2 new BIP investments:

Ontario’s Premier — Dalton McGuinty, winner of BIO’s second annual International Leadership Award — spoke next, highlighting the Ontario Innovation Agenda, including BIP, business tax reductions and recent funding in the Emerging Technologies Fund and the new $100 million for genomics research.

Dr. Nagy also spoke, emphasizing the $100 million of new funding and the value of a peer group of 95 P.I.’s in Ontario working on stem cells and regenerative medicine. Current work focuses on cell type switching without regression to pluripotency.

On to the omelet…

P.S.  First time here at the Cross-Border Biotech Blog?  Welcome! Check out who we are, check out our Trends in 2009 series, or hit the search and navigation tools on your right and see if you see anything interesting.

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Wednesday Brain Dump: Around the World Edition

States Step in to Ban Stem Cell Research

For those in Canada and the UK who were worried that Obama’s move to restore U.S. federal funding for stem cell research would create a 50-state mecca, I have good news:

Reuters reported yesterday that several U.S. states — Oklahoma, Georgia, Mississippi, Texas, Arizona and Louisiana — have passed or are considering legislation to outlaw some forms of embryonic stem cell research. 

For legislators in those states who voted for the bans, I have a short educational video to recommend to you:

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Restoring Scientific Integrity to Government Decision Making

In addition to Obama’s announcement today lifting the ban on federal funding of stem cell reasearch, he also issued a presidential memorandum

To ensure that in this new Administration, we base our public policies on the soundest science; that we appoint scientific advisors based on their credentials and experience, not their politics or ideology; and that we are open and honest with the American people about the science behind our decisions.

To which I can only say: thank goodness. 

Read the full memorandum after the jump…

Canadian Budget Reaction Boils Over

A meeting this week between the Canadian Association of University Teachers and Gary Goodyear, Canada’s Minister of Science and Technology descended into a shouting match over cuts to research funding announced in Canada’s 2009 federal budget.

Interestingly, the Minister focused on a point I made last week — that the Canadian approach lately has centered on commercialization:

Mr. Goodyear, a chiropractor from Cambridge, Ont., said the government has been steadily investing in science and technology since 2006, with a new emphasis on commercialization…

I think commercialization is a worthwhile investment; but funding commercialization at the expense of Canadian research is a major  blunder, for the following reasons:

  1. There is no commercialization without research.  Researchers from Boston or San Francisco or Edinburgh will not suddenly move here to start their companies because of extra NRC-IRAP funding.  If the developments aren’t made here, the companies won’t be formed here either.
  2. Research is an area in which Canada punches above its weight.  Check out our Friday Science Reviews and you will see international headlines and top tier journal articles.  However, a lot of hard reputational work is undone by the kind of international reaction generated by the 2009 budget.
  3. The timing is bad.  The increased research funding provided by the U.S. budget and stimulus makes for a terrible comparison.  Plus, Obama is poised to lift the U.S. federal funding ban on stem cell research tomorrow (Monday); and this is an area where we have benefited from an extra structural advantage that is about to be erased (as observers in the UK have already noted).

So, Mr. Goodyear, by all means focus on commercialization.  We can (and will) quibble about that implementation another time.  But in the meantime, restore the research funding that makes us a world-class producer of scientific innovation.

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Wendesday Brain Dump: January 28

Things that caught my eye this week:

The FDA made Geron very happy; Sarkozy made French scientists very unhappy.

Here at home, some regulatory milestones for Oncolytics, Welichem and Pfizer Canada.

Europe’s R&D intensity (spending as a percentage of GDP) was stagnant overall from 2000 to 2006, but at least a few detractors are out of commission.

And last, since we don’t want to dwell on the negative, some advice from PwC on transfer pricing and other more general approaches to weathering the downturn.

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