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

Category Archives: Richard Chan

Friday Science Review: October 23, 2009

A lucky find and two very different genomics projects…

Connective Tissue Disorder Linked to Defects in Ltbp4:  A McGill University researcher collaborating on two independent projects, one from Washington University School of Medicine and the other from New York University School of Medicine, made the coincidental link between the two after realizing that the tissue defects were identicalDr. Elaine Davis, an electron microscopy expert at McGill, analyzed tissue from children born with abnormally developed lungs, gastrointestinal and urinary systems, skin, skull, bones and muscles.  The underlying cause is a connective tissue disorder called cutis laxa that also causes skin to hang loosely from the body.  At the same time, Dr. Davis was analyzing tissue taken from Ltbp4 gene knockout mice from New York University when she realized that the connective tissue defects in the human and mouse samples were identical.  This connection was confirmed when they sequenced the Ltbp4 gene in human patients and discovered recessive mutations.  With this discovery, they now have a molecular target to understand the disease and to design therapeutic strategies.  The study is reported in The American Journal of Human Genetics.

A Deep-sea Microbe Genome: The microbe, SUP05, lives in the deep ocean “dead zone” where oxygenated water is minimal. It survives by using other compounds instead of oxygen, such as nitrates, sulphates and metals.  A recent surge in population suggests an expanding low-oxygen ocean ecosystem and is an indicator of global climate change.  University of British Columbia professor Dr. Steve Hallam and his research group analyzed the entire genome of SUP05 and identified a number of genes mediating carbon assimilation, sulfur oxidation, and nitrate respiration.  This study provides the first insight into the metabolism of these microbes and their effects on nutrients and gases in the deep-ocean ecosystem and will also lead to further understanding of their ecological and biogeochemical role.  The report appears in this week’s edition of Science.

Allelic Expression Genomic Map: Illumina genomics technology was used in this study to map global allelic expression differences associated with cis-acting variants.  Cis-acting elements can affect gene expression and variations due to single nucleotide polymorphisms (SNPs) explain a large percentage of the phenotypic differences in the population.  It is very informative to have this global map of the cis-acting variants and helps researchers identify variants associated with diseases.  To demonstrate this, they finely mapped cis-regulatory SNPs in a region in chromosome 8 associated with lupus.  The study was performed by Dr. Tomi Pastinen and his Genome Quebec team at McGill University and the report was published in Nature Genetics.

DNA Repair Suppresses c-Myc Lymphoma:  Overexpression of c-Myc in B cells is associated with lymphomas but requires secondary mutation events for the disease to develop.  In this study, immunologist Dr. Alberto Martin and his research team at the University of Toronto identified that the DNA repair protein, Msh2, plays an important role in mitigating c-Myc associated cancer.   To demonstrate this, they generated mice that overexpress c-Myc but with Msh2 mutations such that they are deficient in DNA mismatch repair.  These mice rapidly develop B cell lymphomas, which suggests that Msh2-dependent DNA repair actively suppresses c-Myc associated oncogenesis.  The report appears in the early edition of The Proceedings of the National Academy of Sciences.

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Friday Science Review: October 16, 2009

A mixed bag of research reports but nonetheless important and significant…

How MS Drug Works: Glatiramir Acetate (COPAXONE®, Teva Pharmaceuticals) is used for the treatment of patients with Multiple Sclerosis, however, it is not clear how this drug works.  In this new study, researchers demonstrate that glatiramir acetate can regulate the formation of myelin, the protective sheath around nerve fibers that is compromised in MS patients.  Glatiramir acetate induces the formation of helper immune cells that produce nerve promoting molecules, which in turn stimulate the myelin repair process. The study was led by Dr. V. Wee Yong at the University of Calgary and appears in this week’s issue of The Proceedings of the National Academy of Sciences.

New Target to Fight Diabetes: In genetic knockouts of the Lkb1 gene specifically in beta cells, the insulin producing units in the pancreas, the knockout mice exhibited an increased number of beta cells that were also larger than normal with greater amounts of insulin.  When they challenged the knockout mice with a high-fat diet to try to induce diabetes, the mice responded and kept blood glucose levels down.  Lkb1 is a tumor suppressor gene that was also known to be involved in energy metabolism but it was unclear whether the Lkb1 protein was associated with diabetes.  Dr. Robert Screaton’s group at the Children’s Hospital of Eastern Ontario Research Institute answered this question in a report appearing in this week’s Cell Metabolism.  Also noteworthy is that a research team from Israel published a similar study leading to the same conclusions.  With these surprising and dramatic results, Lkb1 may represent another therapeutic avenue to treat or prevent diabetes.

Sialyltransferase Crystal Structure Solved: Many important proteins, lipids or sugars are modified by the addition of sialic acid and these steps are essential for a number of processes including cell recognition, cell adhesion and immunogenicity.  The key enzyme responsible for catalyzing this reaction is a set of related sialyltransferases (ST).  In a Nature Structural and Molecular Biology report published this week, Dr. Natalie Strynadka (University of British Columbia) describes solving the crystal structure of ST and provides the first detailed understanding of the enzyme.  Without getting into any molecular jargon, suffice it to say that the structural data brings insight into how the enzyme works and how it achieves specificity, which is useful knowledge for developing prospective inhibitors.

Power of Pheromones: Researchers removed the pheromone-producing cells in fruit flies (male or female) and found that these flies were extremely attractive to normal male fruit flies and also flies of other related species.  This contradicts the notion that these chemical signals simply attract one individual to another.  Instead, they are part of a complex signaling system used by the flies to recognize and distinguish sexes and species.  Other unusual behaviour by male fruit flies without pheromones included trying to copulate with each other’s heads.  Dr. Joel Levine and his team at the University of Toronto (Mississauga) describe their research in detail in this week’s edition of Nature.

Beta-globin Switch: A proteomics screen was used to identify the enzyme G9a as the interacting partner of NF-E2, which act together to control expression of the beta-globin genes in red blood cell development.  This study provides a clearer understanding of the molecular determinants controlling embryonic expression of beta-globin where G9a acts as a repressor and its transition to adult beta-globin expression where G9a promotes expression.  The research team at the Ottawa Hospital Research Institute was lead by Dr. Marjorie Brand and the study appears in the early online edition of the Proceedings of the National Academy of Sciences.

Friday Science Review: October 9, 2009

Breast cancer, genomics and two cover stories in prestigious journals…

Cancer Evolution and Progression:  Scientists at the BC Cancer Agency have sequenced and compared the entire cancer genome of a metastatic tumour versus the primary breast tumour that originated nine years earlier.  They used next generation DNA sequencing technology to reveal 32 mutations in the metastatic cancer but surprisingly only five of these were present in the original tumour.  Six mutations were present at lower frequencies in the primary tumour, 19 were not detected and 2 were undetermined.  These differences may provide clues about how cancer becomes resistant to therapy or how a tumour switches to aggressive metastasis that spreads to other sites in the body.  The study demonstrated that cancers evolve and that there may be significant heterogeneity within the tumours.  These findings emphasize the importance of ongoing research efforts to sequence all cancer genomes and buttress arguments in favour of personalized medicine.

The study was lead by Dr. Samuel Aparicio at the BC Cancer Agency and appears as the cover story in the latest edition of Nature.

Honey, I shrunk the lab: The “lab-on-a-chip” concept has been in use for a number of years but Dr. Aaron Wheeler’s Microfluidics Laboratory at the University of Toronto has designed a new module for use in breast cancer detection and care.  The hand-held sized device can extract and quantify estrogen in a very small sample size – as little as a 1 microliter sample of tissue or blood – by using electrical charges to move liquids around in a precise manner over a microchip.  Current methods require a much larger sample, about the size of a penny, which is often impractical to obtain.  Since elevated estrogen levels are associated with breast cancer risk and pathogenesis, this new device could be used at point-of-care to screen at-risk patients or to monitor therapies and provide results within minutes instead of days.

Dr. Wheeler collaborated with Dr. Robert Casper (University of Toronto and Samuel Lunenfeld Research Institute) on this project, which garnered the inaugural cover story in the new journal, Science Translational Medicine.

Genome Map Upgrade: Researchers have generated a comprehensive structural map of the human genome in identifying and marking regions that are duplicated or deleted, the so-called copy number variation (CNV).  Genetic variation is what makes us different and certain areas of the genome reflect these differences whereas other genetic regions show very little variation and are likely essential function genes.  It also provides important clues to understanding evolution and provides the foundation for future research in developing personalized medicine.   The international study was co-lead by Dr. Stephen Scherer at The Centre for Applied Genomics (Hospital for Sick Children, Toronto) and provides the following comments:

“The scale of this current project is 100 times the scale of all others.”

“Previous work in this field would be like a paper fold-up map; this advancement is like a GPS that takes you where you need to go. It allows you to navigate the landscape of the genome, from its peaks where there is vast genetic variation, to its valleys devoid of it.”

“Variation is indeed the spice of life and we now know that nature buffers this variation by using CNVs. We are harnessing this knowledge to fight disease.”

Dr. Scherer is also involved in maintaining the Database of Genomic Variants, which provides researchers around the world access to a curated catalog of CNVs.  Details of the research report appear in the advanced on-line edition of Nature.

Congratulations to McGill University alumni Jack Szostak and Willard Boyle for winning the 2009 Nobel Prize in their respective disciplines.

Dr. Jack Szostak started at McGill when he was 15 years old and graduated in 1972, specializing in cell biology.  This was the start of a brilliant research career where he co-discovered how telomeres and telomerase protects chromosomes from losing genetic material during cell division.  He shares the 2009 Nobel Prize for Medicine.

Dr. Willard Boyle completed his BSc (1947), MSc (1948) and PhD (1950) from McGill.   He shares the Nobel Prize for Physics for the 1969 co-invention of the charged-couple device (CCD) that is used in today’s digital photography technology.

Friday Science Review: October 2, 2009

Prostate cancer and H1N1 updates…

Nanotechnology is Coming:  A research study by a group of University of Toronto engineers, nanoscientists, and pharmaceutical specialists has garnered a lot of media attention this week describing the use of nanomaterials in microchip technology to create a highly sensitive biosensor.  In the more technical report published in Nature Nantotechnology this week, they describe a special nanostructuring technique arranged in an array architechture to expand the dynamic range and sensitivity of the system for nucleic acid and protein biodetection.  The microchip is small, fast, and super sensitive.

In an earlier publication in ACS Nano, they applied their nanotechnology to detect prostate cancer biomarkers.  They demonstrated the accuracy, sensitivity and speed of the non-invasive test, which they are trying to package into a small hand-held device that can readily conduct testing at the point-of-care.  Of course, the application of this technology goes far beyond prostate cancer and can be adapted to detect other cancer biomarkers, HIV and other diseases.   Nanomaterial, nanotechnology, nanomedicine – these are hot words that you will hear about more frequently in the near future.

The research was lead by University of Toronto scientists, Drs. Shana Kelley and Ted Sargent.  A spinoff company based on the molecular diagnostic platform, tentatively called GenEplex, is in the works with the support of the Ontario Institute for Cancer Research’s Intellectual Property Development and Commercialization Program.  Also, the Ontario Genomics Institute is funding a microRNA application of the technology to the tune of almost $1 million.

In other prostate cancer research news:

Targeting IGF-1R:  Researchers targeted the Insulin-like growth factor-1 receptor (IGF-1R) with antisense technology to suppress IGF-1R expression in prostate cancer cells.  They found that by inhibiting IGF-1R signaling activity, the cancer cells grew more slowly but also increased their rate of cell death.  This is the first preclinical proof-of-principal that antisense therapy targeting IGF-1R in prostate cancer may be a viable treatment route and warrants further investigation.

The study was conducted by Dr. Michael Cox at the Vancouver Prostate Centre and published in this week’s editon of The Prostate.

Fatty Acids Promote Prostate Cancer: The hormone androgen, and its androgen receptor partner, have been shown to contribute to prostate cancer progression.  In this research report, researchers at the University of British Columibia suggest that elevated fatty acid (arachadonic acid) levels in the tumors may lead to increased activation of steroid hormone synthesis and contribute to the progression of the cancer.  Therefore, they recommended that fatty acid pathways should also be targeted as part of a therapeutic approach to treating prostate cancer.

Dr. Colleen Nelson led the research team at the Vancouver Prostate Centre and published the report also in this week’s edition of The Prostate.

H1N1 Update: Following last week’s “seasonal flu vs. swine flu” vaccination story, the Public Health Agency of Canada reviewed their own data and soon declared their position on the yet unpublished study saying that “there is no link between having a seasonal flu shot and developing a severe bout of pandemic flu.”  More to follow on this as the controversial study should become public next week.

In other H1N1 news:

Big Pharma gets Immunity: As increasing H1N1 cases emerge and Health Canada is being encouraged to expedite the approval of H1N1 vaccines, the Public Health Agency of Canada is following other countries in stating that they will protect GlaxoSmithKline, the maker of the vaccine, from any lawsuits arising from potential side effects.

Surgical Masks are Adequate: Healthcare workers should be encouraged by a study comparing standard surgical masks versus N95 respirator in protecting against flu viruses (swine included).  In the randomized controlled study, conducted by flu expert Dr. Mark Loeb at McMaster University, 446 nurses from eight hospitals in Ontario were equally distributed to wear either sugical masks or fit-tested N95s.  The results showed that there was an insignificant difference (23.6%, surgical mask vs. 22.9%, N95) in the number who contract the ‘flu’ during the course of the season.  However, this study is sure to raise more debate within the healthcare community as unpublished work in China found that N95 masks can cut the risk of catching the flu virus by 75% while surgical masks offer no protective effect.  Dr. Loeb’s study is published in the early edition of JAMA.   A commentary on this issue is also provided by the U.S. Centers for Disease Control and Prevention.

Benefits of Handwashing? And if you are not confused enough about how to avoid catching the virus, consider this article in CMAJ questioning the benefits, due to lack of scientific evidence, of hand washing in preventiing the transmission of influenza viruses.

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Friday Science Review: September 25, 2009

A quiet week for journal publications but there were a few significant research related activities…

Canadian Stem Cell Charter: At the recent World Stem Cell Summit in Baltimore, Canada stepped up and demonstrated why we are one of the leaders in stem cell research.  This time it was not a lab discovery but the Canadian Stem Cell Foundation’s launch of a charter outlining ethical principals and a code of conduct to guide stem cell research in a responsible and ethical way.

The Stem Cell Charter upholds the following principles:
• Responsibility to maintain the highest level of scientific quality, safety and ethical probity
• Protection of citizens from harm and the safeguarding of the public trust and values
• Intellectual Freedom to exchange ideas in the spirit of international collaboration
• Transparency through the disclosure of results and of possible conflicts of interest
• Integrity in the promotion and advancement of stem cell research and therapy for the betterment
of the welfare of all human beings

Bartha Knoppers, a bioethicist at McGill University’s Centre of Genomics and Policy, authored the charter in collaboration with a working group of scientists, patients, ethicists and laypeople.  She describes the purpose of the charter:

“There have been a lot of spurious claims in this area, people doing the first of this or the first of that, and it not being true,”

“It’s a wake-up call to scientists to remind them that if they want to work in this field, they have to do so under a scientific code of conduct and it’s to reassure the public that this is not the Wild West.”

“We’d like to keep it a credible science,”

“We’d like to keep it a science that merits public investment and public funding.”

Signing on (www.stemcellcharter.org) and adhering to the charter is one way of doing just that.  It is also a way for the public to show their support for stem cell research and to make their voices heard.

By the way, September 23rd was Stem Cell Awareness Day!

The Michael J. Fox Foundation for Parkinson’s Research (MJFF): This was mentioned in yesterday’s post on this blog.  Michael J. Fox announced the charity status of the Canadian arm of his MJFF for Parkinson’s Research in association with The McEwen Centre for Regenerative Medicine (MCRM) and Toronto Western Hospital (TWH).  I just want to emphasize the significance from a research perspective.  He is an advocate for stem cell based therapy and his Foundation promotes and emphasizes the sharing of scientific information to facilitate quicker results – “We don’t just fund research.  We fund results.”

Flu shot increases risk of H1N1 virus:  An unpublished Canadian study is garnering attention by suggesting that a seasonal flu shot may actually increase an individual’s chances of catching the H1N1 virus.  The report is still under peer-review and the details are not available but it was enough for Ontario to modify its flu vaccination program this season.  Younger people will not be offered the seasonal flu vaccine until they receive the H1N1 vaccine, which will not be available until mid-November.  Other provinces are also considering making some changes to their programs.

The CDC and WHO are looking into this controversial study but are taking a cautious stance, refraining from acting too quickly:

“The reason why this may be different in Canada and in this particular study than in other places of the world is not yet identified. It may be a study bias, it may be that something is real,”

“None of the other countries have been able to find anything like that”

This enhancing effect would be unusual for flu viruses but not completely new from a biological perspective.

Dr. Danuta Skowronski of the British Columbia Centre for Disease Control and Dr. Gaston De Serres of Laval University led the research study.

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Friday Science Review: September 18, 2009

Some “brainy” research this week…

brainy

Curiosity Driven <=> Intelligence: There is new evidence that “fostering curiosity should also foster intelligence and vice versa.”  Researchers have discovered what they believe is the region of the brain, the dentate gyrus in the hippocampus, that is responsible for generating curiosity.  They also identified that the interaction between the neuronal calcium sensor-1 protein (NCS-1) with the dopamine type-2 receptors (D2R) is what triggers the curiosity-like behaviour.  In the investigation lead by  Dr. John Roder at the Samuel Lunenfeld Research Institute, they modestly overexpressed NCS-1 in the dentate gyrus region of mice and observed an exploratory type behaviour, interpreted as curiosity driven.  Researchers also noted improvements in intelligence as demonstrated by the performance of the mice in spatial memory tests.  Conversely, these phenotypes were reversed when the mice were treated with a drug that inhibits NCS-1 from binding to D2R.  This study appears in the latest edition of Neuron.  So go ahead and let your mind go free…

Dream on: Here’s how you can enjoy your nice dream twice as long – have your doctor perform deep brain stimulations (DBS) on you!  When scientists specifically stimulated an area of the brain responsible for the deep REM (rapid eye movement) sleep in parkinsonian patients undergoing a surgical procedure, they observed an extended period of brain wave activity consistent with REM sleep.  This is the “dreaming sleep” that we enjoy and provides the refreshing recharge we all need.  Sleep specialist Dr. Brian Murray was the lead investigator in the study conducted at Sunnybrook Health Sciences Centre and published in Annals of Neurology “This finding is significant for patients as it confirms, in principle, that we can selectively adjust different stages of sleep and this may make a big difference to sleep quality as well as other affected neurological functions and brain health.” Now we just need a longer day to accommodate the extra sleep!

Helping the vision impaired to seeevSpex, is an innovative sunglass-type device that can help those who are nearly blind to see via a digital image captured on a high resolution camera and played on a small LCD screen projected onto the user’s eyes.  The key feature is that the image is first processed and customized to the user before it is presented to the part of the vision that is most functional, maximizing “vision.”  The device includes features such as zoom and recording capabilities that can be played back instantly in case the viewer missed something.  Many people with different types of visual impairments will be able to benefit greatly from this technology.

evSpex was developed by eSight Corp in Ottawa with help from Dr. Réjean Munger, a senior scientist at the Ottawa Hospital Research Institute.

Friday Science Review: September 11, 2009

Two great medical discoveries…

Stayin’ Alive:  During a stroke, for example, neurons deprived of oxygen undergo cell death.  In a recent discovery lead by Dr. Michael Tymianski’s team at the Krembil Neuroscience Centre at Toronto Western Hospital, the protein TRPM7 was found to play a critical role in mediating this detrimental effect.   After suppressing TRPM7 expression in a localized region of a rat’s brain, they simulated a stroke by cutting off blood flow to the brain for 15 minutes.  The subsequent analysis revealed a complete lack of tissue damage compared to rat brains expressing TRPM7.  The resistance to death by cells lacking TRPM7 even preserved the brain’s cognitive function and memory performance following the ‘stroke’.  This may have tremendous implications for preventing further cell damage following ischemia in any tissue and is not necessarily limited to the brain, although it is yet to be tested elsewhere in the body

Details of the discovery are reported in the latest edition of Nature Neuroscience.

Insulin Resistance Gene Discovery: An international effort led by Dr. Robert Sladek and Dr. Constantin Polychronakos at McGill University performed a genome-wide comparison and identified a single nucleotide variation in the genetic region near the IRS1 gene that is associated with insulin resistance and hyperinsulinemia.

Dr. Sladek explains it best:

“It’s a single-nucleotide polymorphism (SNP, pronounced ‘snip’), a single letter change in your DNA,” said Sladek. “What’s interesting about this particular SNP is that it’s not linked genetically to the IRS1 gene in any way; it’s about half-a-million base-pairs away, in the middle of a genetic desert with no known genes nearby. In genetic terms, it’s halfway from Montreal to Halifax. And yet we can see that it causes a 40-per-cent reduction in the IRS1 gene, and even more important, a 40-per-cent reduction in its activity. Which means that even if insulin is present, it won’t work.”

IRS1 is known to be the key signalling protein involved in the cell’s initial response to insulin.  This recently discovered variant allele affects the level of IRS1 protein expressed and reduces the capacity of the cells to respond to insulin. Unlike other diabetes risk genes that affect insulin production in the body, this is the first that is known to suppress insulin stimulation in the cells.

The research article appears in the early online edition of Nature Genetics.

Friday Science Review: September 4, 2009

Potential future therapeutic options…

Dabigatran versus Warfarin: Dabigatran (PRADAX®, Boehringer-Ingelheim) was compared with warfarin (a commonly used anti-coagulant) in a large scale study for the treatment of patients with atrial fibrillations.  The trial demonstrated that the group of patients taking the higher dose of Dabigatran had significantly reduced risk of stroke compared to patients on warfarin but with similar risk of hemorrhaging.  With a lower dose of Dabigatran, they achieved protection from strokes that was similar to that afforded patients using warfarin but with a significantly reduced risk of major bleeding.  Dabigatran is the first alternative therapy option to warfarin treatment showing efficacy and improved safety to patients.  The global study was headquartered out of Hamilton at McMaster University and Hamilton Health Science Centre and appears in this week’s The New England Journal of Medicine.

Drug combo for Bell Palsy: Combinatorial therapy may be a better treatment method to improve the facial paralysis symptom of Bell Palsy patients. In the study lead by Dr. John de Almeida at Sunnybrook Health Science Centre, they compared the standard treatment with corticosteroids alone versus corticosteroids supplemented with antiviral drugs.  It is thought that a herpes infection is likely the cause of the disorder.  As the patients appeared to have experienced a slight incremental benefit from the combo therapy, the researchers will continue their study to provide a definitive answer.  The report was published in the current issue of the Journal of the American Medical Association (JAMA).

Key finds from studying protein structure:

  • The RAF family of proteins is an integral component of the RAS signaling module involved in cell growth, differentiation and survival.  This new structural study on BRAF revealed that its catalytic function is regulated by a “side-to-side” dimerization mode.  Interestingly, a mutation found in oncogenic versions of BRAF is located in this dimerization interface and promotes aberrant activation.  Surely, the side-to-side dimer interface of BRAF will be a potential target for therapeutic intervention against BRAF-dependent tumorigenesis.  This exciting research was lead by a collaborative effort between Dr. Frank Sicheri at the Samuel Lunenfeld Research Institute in Toronto and Dr. Marc Therrien at Université de Montréal and published in the early edition of Nature.
  • New insight into how bacteria can steal iron from its host was revealed through structural studies of the bacteria’s transferrin receptor.  The bacterial transferrin receptor binds to the host’s iron containing transferrin protein, extracts the iron and transports it across the membrane.  When they mutated a critical residue at the interface of this interaction, binding was completely abolished.  Perhaps these results from Dr. Anthony Schryvers’ research team at the University of Calgary will lead to future directions for antimicrobial therapeutics.  The study was published in the recent edition of Molecular Cell.

Nervous system development in today’s issue of Cell…

  • Researchers revealed how the neural-specific SR-related protein of 100 kDa (nSR100) is responsible for facilitating alternative transcript splicing specifically in the nervous system.  nSR100 is required for neural cell differentiation and contributes to the greater complexity of the vertebrate nervous system.  The research was lead by Dr. Benjamin Blencowe at the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research.

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Friday Science Review: August 28, 2009

A Montreal flavour this week…

Critical link between EGFR and Src oncogenes: On the heels of last week’s Friday Science Review post on Stat3 in breast cancer, Dr. William Muller’s research team at McGill University has published another significant find linking well known oncogenes, Src and EGFR/ErbB2.  Among their results, they demonstrated how Src can interact with some mutant EGFR receptors (identified in lung cancers) but not with wild type EGFR.  When a Src inhibitor was applied to cells expressing mutant EGFR, it attenuated the cancer-inducing potential of these EGFR mutants.  This suggests that Src is an important enzyme in the EGFR mutant signaling pathway and may present an alternate pathway to combat cancer cell resistance to EGFR inhibitors.

Details of this study are described in this week’s Molecular and Cellular Biology.

MET oncogene in breast cancer: Next door to the Muller Lab at the new Goodman Cancer Centre in Montreal is Dr. Morag Park and her research team who recently generated a mouse model to mimic and study the Met oncogene in breast cancer.  The results were a complex cancer phenotype where gene expression and histological profiles demonstrated similarities to aggressive human breast cancers expressing Met.  Whereas prior to their study, Met was only correlated with poor outcome in breast cancer patients, this mouse model provides the specific link and identifies clinical cases where anti-Met therapy may be beneficial.

You can read more about it here in Proceedings of the National Academy of Sciences.

Key proteins in Natural Killer Cells: Also this week, Dr. André Veillette’s lab at the Institut de recherches cliniques de Montréal (IRCM) generated new insight into how Natural Killer Cells combat cancers of the blood, such as leukemias and lymphomas, or virus-infected blood cells.  As part of our immune system, the defense function of Natural Killer Cells requires three small proteins named SAP, EAT-2 and ERT that are unique to immune cells.  The proteins relay information from the cell surface SLAM family receptors to direct immune activities.  These data may eventually lead to pharmacological methods to increase the activity of Natural Killer Cells in destroying blood cancer cells or virus-infected cells.

Veillette’s lab generated knock-out mice missing all three proteins, which led to their findings, which are published in the latest edition of Nature Immunology.

p53 is regulated by JNK: p53 is a tumor suppressor protein that plays an important role in regulating cell growth and survival.  Its critical functions in the cell require p53 to be highly regulated through multiple layers of control, both to turn on and to turn off the protein’s activities.  One such method recently described in Proceedings of the National Academy of Sciences is through phosphorylation by the enzyme JNK.  This phosphorylation protects p53 from being targeted for destruction, thereby allowing p53 complexes to form and continue with their gene activating activities.

This research project was a collaboration between the Burnam Institute in San Diego and Dr. Katherine Borden’s team at the Université de Montréal.

Jurassic Park (for real?): Can you convert a chicken embryo to develop into a dinosaur?  No, this is not the makings of a movie but the idea of paleontologist Hans Larsson of McGill University who is proposing to try to make it work.  The theory is that by manipulating or swapping certain “switch” genes during the chicken embryo’s development, he can reproduce some features of a dinosaur.  He does not actually intend to hatch live prehistoric animals – for obvious reasons:

“It’s a demonstration of evolution,” said Larsson, who has studied bird evolution for the last 10 years.

“If I can demonstrate clearly that the potential for dinosaur anatomical development exists in birds, then it again proves that birds are direct descendants of dinosaurs.”

“We’re not going to hatch a T. rex or something,” Larsson chuckles.

The idea came to him after meeting Jack Horner, author of the book “How to Build A Dinosaur” and the technical advisor behind the Hollywood version of Jurassic Park.

Come back to the Friday Science Review (perhaps in a few years) for an update on the “chickensaurus” experiment…

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Friday Science Review: August 21, 2009

This week… cancers, brains, and fruit flies.

Combinatorial therapy to fight melanoma: Malignant melanomas are aggressive cancers that are highly resistant to chemotherapy, possibly due to high levels of Bcl-2 family anti-cell death  proteins.  Although the small molecule inhibitor, ABT-737, is effective against Bcl-2 family proteins in other cancers, it is not very effective in melanoma cases.  The reason may be due to overexpression of another protein, Mcl-1, which confers resistance to ABT-737.  When  Dr. Victor Tron’s group at Queen’s University combined ABT-737 treatment with inhibitions of Mcl-1 by way of siRNA knockdown, the cancer cells lost their resistance and underwent cell death.  These findings, appearing this week in PloS One , suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma.

Understanding Stat3 in Breast Cancer: Elevated Stat3 levels in breast cancer patients often correlate with poor clinical outcome.  To understand how Stat3 may influence cancer progression, a Stat3 knockout mouse was combined with a mouse expressing the mutant form of the breast cancer gene, ErbB2, and predisposed to develop breast tumours.  What the researchers at McGill University found was that without Stat3, breast cancer still developed but the malignancy of the mammary tumours decreased significantly with fewer animals having metastatic lesions in the lung.  Genetic profiling of the tumours showed that without Stat3, angiogenic and inflammatory responses, which often play an important role in the metastatic process, were blunted.  Remember, last week I noted an article on Par6 and TGFb in breast cancer metastasis.

This recent study, hot off the press in Cancer Research, was led by Dr. William Muller, one the early pioneers in using transgenic mouse technology.

Gene expression differences in suicide brains: This is the first study to perform global gene expression analysis on the brains of suicide cases to try to broaden the scope of suicide research to other neurotransmitter systems.  The serotonergic system is well studied as the primary area of the brain involved in suicides but there are likely other contributing factors.  Dr. Turecki’s research team at McGill University performed microarray expression studies on a number of brain tissue samples from the cortical and subcortical regions to identify potentially new molecular pathways involved in depression and suicide.  Their results revealed a number of alterations including genes involved in synaptic neurotransmission, namely upregulation of glutamatergic (excitatory) and GABAergic (inhibitory) related genes in suicide brains.  This report in PLoS One should open the research field into exploring alternate treatment methods and better understanding the development of suicide and depression.

Male hormone discovery: A new male-specific pheromone was identified on fruit flies.  When the researchers transferred some of the compound onto female fruit flies, the male flies were suddenly uninterested.  How did they identify this pheromone?  They exposed a fruit fly to a laser in a MALDI-type mass spectrometer instrument where ions are ejected into the instrument and analyzed.  Some previously unidentified compounds were discovered including this hormone.  The research was conducted at the University of Toronto Mississauga by Joel Levine and Jocelyn Millar and appears in this week’s Current Biology.

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Friday Science Review: August 14, 2009

Great stuff this week in Canadian science news…

A GIFT for MS patients:  An experimental treatment tested in mice with multiple sclerosis was able to reverse the disorder with few side effects.   The new compound is called GIFT15 – a hybrid protein between GSM-CSF and Interleukin-15.  Surprisingly, it produces results that you would not expect from the action of the individual proteins.  GIFT15 causes B-cells to switch from immune responsive into immune-suppressive regulatory cells and this forces MS into remission.  The treatment method takes B-cells from the individual and exposes them in vitro to GIFT15 to convert them to regulatory B-cells before they are injected back into the patient – a form of personalized medicine.

As always, one should be cautious as these experiments were tested in mice and it is unknown how humans would respond .  It does, however, present a new approach to finding a treatment regime for MS and may also lead to similar therapies for other autoimmune disorders.

Dr. Jacques Galipeau led the study at the Lady Davis Institute for Medical Research, McGill University and it is presented in the early on-line edition of Nature Medicine.

An Epilepsy gene discovery:  A mouse that experiences seizures was identified in a mutagenesis screen that led to the discovery of an inactivating mutation in the Atp1a3 gene encoding the Na(+),K(+)-ATPase alpha3 isoform protein.  It is a sodium-potassium transporter protein having important roles in maintaining the electrochemical gradient across cell membranes.  When the mutant gene was augmented with a wild type Atp1a3 gene by breeding the mutant mouse with a transgenic mouse expressing normal Atp1a3, the protein function was rescued and more importantly, the seizures subsided completely.  The human ATP1A3 is almost identical to the mouse protein and studies are underway to try to find a similar mutation in patients.

Dr. Roder’s group at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto published these results in PNAS this week.

New forensic DNA extraction tool:  High quality nucleic acids can now be extracted from the smallest sample size or from highly contaminated samples.  The technology is based on the electrical properties of nucleic acids rather than on the chemical properties that traditional purification methods are based on.  It uses a novel electrophoresis technology called SCODA (Synchronous Coefficient of Drag Alteration), a fancy name for a type of rotating electrical field that selectively acts on long, charged polymers (e.g. DNA).  This electrical field will concentrate DNA while separating it from contaminants.

The research was performed by the biophysics team led by Dr. Andre Marziali at the University of British Columbia.  They have already teamed up with UBC spin-off company, Boreal Genomics to package the technology into a cool-looking device called the Aurora.  It is not surprising that it has garnered a lot of interest from law enforcement groups in Canada and the U.S.   Of course, there are a number of other applications for this technology such as in clinical research for the early detection of diseases or infections.

The research is described in a PNAS paper that will be coming out very soon but here is the UBC press release.  A great example of “Today’s Canadian science = tomorrow’s Canadian start-ups” (…if you caught the tweet last week).

Wow!  Canadians are on a roll… more research published in Proceedings of the National Academy of Sciences. Here are the headlines:

Dr. Jeffery Wrana’s team (Samuel Lunenfeld Research Institute) describes how this signaling pathway is involved in breast cancer metastasis.

Dr. Uzonna (University of Manitoba) reports on why in some cases, vaccination against Leishmaniasis (a parasitic disease) can actually make them more susceptible to future infections.

Dr. Brisson (Université de Montréal) studies the Whirly protein – need I say more?

Dr. Barry Honda (Simon Fraser University) uses Drosophila to help us better understand O-linked N-acetylglucosamine transferase (OGT), which has been implicated in a number of processes including insulin signaling, neurodegenerative disease and cellular stress response.

Dr. Zatorre (Université de Montréal) breaks down how our brain processes sound and suggests that it is similar to the visual system of our brain.

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Friday Science Review: July 31, 2009

My first post… a two week round-up.

New direction for treating obesity:  A study headed by Dr. Hans-Michael Dosch’s group at The Hostpital for Sick Children in Toronto demonstrated that killer T cells in visceral fat are activated to destroy fat cells and control insulin resistance.  With increasing weight gain, however, the killer T cells become overwhelmed as fat cells grow and inflammatory T cells move in.  Although these studies were performed in mice, it appears that humans also have a similar system in place.  The good news is that treatment with an anti-CD3 drug can give the immune system a boost and help reduce inflammatory T cells.  Even better news is that this drug is already in clinical use to protect against organ rejection, which means clinical trials to combat obesity may start as early as next year.  The article was published on-line this week in Nature Medicine.

Cool headed Toucan.  After decades of speculation over the purpose of the toucan’s over-sized beak – from sexual ornament to feeding purposes – researchers at Brock University in Ontario, in collaboration with scientists in Brazil, published an article in Science showing that the toucan’s beak acts as a highly efficient cooling unit.  They have the greatest beak-to-body size ratio and use this large surface area as a heat exchanger (akin to elephants’ ears) to regulate body temperature by modifying blood flow.  If only we had a ‘heat wave’ problem this summer…

Setback in Huntington’s Disease research.  A decade long study concluding with disappointing results was reported in PNAS this week.  Researchers at Laval University and University of South Florida analyzed the brains of HD patients who had undergone neural transplantations about ten years ago as a potential treatment.  Although there were mild clinical benefits, the grafts were short-lived and also had undergone disease-like degeneration.

Barcoding Nemo. As part of the International Barcode of Life Project to identify all plants and animals based on signature DNA sequences, spear-headed by Paul Herbert at the University of Guelph, the ornamental fish was added to the list.  Accurate identification of ornamental fish is important for establishing regulations, conservation practices and tracking origins.  The DNA barcode reference for these fish is based on the cytochrome c oxidase subunit I (COI) gene where 98% of the fish have distinct barcode clusters.  The article was published in PLoS One last week.

Funny etiology: two curious New York high schoolers initiated the project and recruited the Guelph lab, sparking headlines last summer when they discovered that some sushi restaurants were mislabeling cheaper fish as more expensive types.

Other DNA barcoding projects include other fish, butterflies, and birds.  To find out more, visit the Canadian Centre for DNA Barcoding or the International Barcode of Life Project (iBOL).

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