The Cross-Border Biotech Blog

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

Tag Archives: McGill

Friday Science Review: November 6, 2009

Just two stories this week – a cancer pathway and innovative dipsticks…

New Relationship between Tumour Suppressor Genes: Knocking out genes in mice believed to play a tumour inhibiting role would intuitively result in rapid cancer development.  However, it was a surprise to McGill researchers that mice lacking the tumour suppressors 4E-BP1 and 4E-BP2 were refractory to cancer growth.  When they deleted another well known tumour suppressor, p53, then they observed enhanced tumour growth more aggressive than knocking out p53 alone.  These results demonstrate for the first time a cooperative effect between 4E-BPs and p53 and highlight the advantages of indentifying individual molecular profiles to predict responsiveness to therapeutic strategies.  Dr. Nahum Sonenberg, who led the research team at McGill University remarks “this is another fine example how basic research, which intends to provide answers to fundamental questions about molecular mechanisms of cell proliferation, leads to unexpected findings that advance our ability to understand and cure human disease.”  The study appears in this week’s issue of Cancer Cell.

Bioactive Paper Sensors: A simple and rapid method to detect pesticides or toxins in food using innovative test strips was recently developed at McMaster University.  These “dipsticks” can sense the presence of small amounts of pesticides in food and within five minutes, a colour change indicates the level of the contaminant.  Future applications of this technology, with a few tweaks,  include detecting for the presence of food borne bacteria such as E.coli, Listeria, or Salmonella.  The practicality, ease of use without the need for large equipment, and the ability to get almost immediate results are huge advantages of the dipsticks to provide rapid screening and could play a role in curbing future outbreaks.  Dr. John Brennan’s team describes their research in the latest issue of Analytical Chemistry.

Bookmark and Share

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: 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: 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…

Bookmark and Share

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.

Share Button

Friday Science Review: March 6, 2009

Cool Canadian science stories this week…

Stem Cells: The big Canadian science news this week was the report by Dr. Nagy’s lab at the Lunenfeld that they have found a much safer way to make pluripotent stem cells from adult tissue.  Their publication (co-authored with Keisuke Kaji’s team at the University of Edinburgh) appeared in Nature this week.

Also on the stem cell front, Dr. Kremer, the co-director of the Musculoskeletal Axis of the Research Institute of the McGill University Health Centre, used Interferon gamma to induce the differentiation of mesenchymal stem cells into osteoblasts in vitro, and that IFNγ knockout mice also show reduced bone density and that isolated mesenchymal stem cells from the knockout mice show a differentiation defect.  Long story short: a potential new target for improving bone density.

Clinical Trials: Good news for GSK and for scientists at McMaster University, who showed that GSK’s Mepolizumab (pdf), an anti-IL5 humanized antibody that blocks eosinophil production, helps severe asthmatics improve asthma and reduce their need for prednisone by close to 90 per cent, a result that was seconded by a group in the UK.

Nanotechnology Costs: We noted a few weeks ago that there were changes coming to nanotechnology regulatory environment, and now researchers in BC and Minnessota estimate that testing the toxicity of existing nanomaterials in the United States could cost between $249 million and $1.18 billion and that full-scale testing could take decades to complete. They propose a tiered approach, similar to the EU’s REACH program for testing toxic chemicals, to define priorities.  Hat tip to ScienceInsider.

Hosted Services: Canadians, being hospitable types, are hosting World Diabetes Congress in Montreal in October, as well as a new Occupational Cancer Research Centre — charged with “improving knowledge and evidence to help identify, prevent and ultimately eliminate exposures to cancer-causing substances in the workplace.”

Musical Chairs: A group at Ryerson University’s centre for learning technologies in conjunction with the science of music, auditory research and technology (SMART) lab have developed a chair that allows the hearing-impaired to experience music by using the skin as a hearing membrane. 

Global Issues: An Amazon drought caused a major release of carbon dioxide; but don’t worry, because we’ll find a new planet in no time.  Sound painful? Don’t worry — a spoonful of sugar really does help the medicine go down.

Bookmark and Share

Personalized Medicine: Local to Global

Two local developments in personalized medicine in Canada, one at the forefront of global efforts, one making recommendations on how to play catch-up:

Read more of this post

Follow

Get every new post delivered to your Inbox.

Join 130 other followers