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Friday Science Review: April 16, 2010

An amazing week of Canadian research advancements…

Cancer Genome Project is Well Underway: The Ontario Institute for Cancer Research (OICR), who is leading the International Cancer Genome Consortium (ICGC), published a report this week in Nature outlining the international effort to sequence 25,000 cancer genomes – 500 genomes from each of the 50 most common cancers such as breast, colon, liver, lung, and pancreatic cancers.  Some partial datasets are already available to the global research community at www.icgc.org.  This is truly a Herculean effort that is only possible because of the international collaborative effort of over 200 members around the globe.  Whole cancer genome sequencing will provide a fundamental base to advance personalized medicine to the next level.  Here is the original OICR press release and you can read a more comprehensive ‘Scientific American’ style news feature article on the cancer genome project here in the same issue of Nature.

Seek and Destory: Non-Hodgkins lymphoma cancer is taking a big hit from a newly discovered compound that destroys lymphoma cells.  The small molecule compound targets and blocks a transcription factor called BCL6, which is responsible for half of non-Hodgkins lymphoma cases.  Scientists started with the 3D structure of the BCL6 protein and used computer-aided drug design to perform in silico screening of over a million compounds.  They eventually narrowed it down to this one compound that proved to be efficacious and also non-toxic.  Dr. Gilbert Prive at the University Health Network led the innovative project that demonstrates the success of a computational approach to drug design and the ability to target transcriptions factors with minimal side effects.  Read all about it! – in the free full text article in Cancer Cell.

Divide and Conquer: Cell division is a complicated process with the synchronized dance of chromosomes segregating to each new cell.  It is a poorly understood process but research is this field is advancing with the discovery of new essential proteins involved in cell divisionDr. Laurence Pelletier (Samuel Lunenfeld Research Institute) and his collaborators in Europe used a combination of RNAi tools and mass spectrometry techniques to identify the components of protein complexes involved in cell division.  As cancer cells are hyperactive dividing cells, this new information will also aid in the advancement of cancer targeting therapeutics.  The study appears in the journal Science.

The Missing Link: Many have suspected that there must be some link or relationship between stress, anxiety and depression.  Now there is molecular evidence that this is true.  The connection involves the interaction between corticotropin releasing factor receptor 1 (CRFR1) and certain types of serotonin receptors (5-HTRs).  CRFR1 activity leads to stress related anxiety and it also stimulates an increase in the number of 5-HTRs in the brain, which can lead to signaling abnormalities causing depression.  The team headed by Dr. Stephen Ferguson at the University of Western Ontario also developed a small molecule inhibitor that blocks 5-HTRs.  Let’s hope this inhibitor and knowledge of the molecular links lead to more effective treatments for these disorders.  Check out the free full-text article in Nature Neuroscience.

Smart Buggers:  Understanding how bacteria become resistant to last-resort antibiotic drugs just got a boost from a McMaster University study.  Vancomycin resistant methicillin-resistant staphylococcus aureus (VMRSA), also known as the hospital superbug, is a rapidly growing problem with limited effective solutions.  The research team identified the histidine kinase VanSsc protein as the direct vancomycin detector in bacteria, which then triggers the expression of three genes that provide the drug resistance.  This is the first important step in redesigning antibiotic drugs to effectively fight these little buggers.   Dr. Gerry Wright and his collaborators published their exciting work in Nature Chemical Biology.

Not Just a Bad Golf Shot: Scientists have identified mutations in the SHANK3 gene that are associated with schizophrenia.  SHANK3 is a scaffolding protein involved in the formation of the synapse and maintains the structure of nerve cells.  Dr. Guy Rouleau’s team at the Université de Montréal discovered the new mutations (R1117X and R536W) in two families with schizophrenia patients where one of these families had three affected brothers.  Further molecular and genetic studies in zebrafish models confirmed that the R1117X mutation causes behavioural defects.  Earlier studies linked SHANK3 mutations to autism, which suggests that there is a molecular connection between the two neurological disorders.  The findings are reported in this week’s edition of the Proceedings of the National Academy of Sciences.

Gene Therapy is Still Alive: The promise of gene therapeutics to cure diseases may not have lived up to the hype presented a decade ago but there are still some hopeful successes using gene therapy.  One recent example comes from Laval University where researchers repaired the defective dystrophin gene responsible for Duchenne muscular dystrophy (DMD). In some cases of DMD, the dystrophin gene is misread causing a frame-shift mutation.  These frame-shift mutations may be targeted and repaired by enzymes called meganucleases.  A proof-of-principle project by Dr. Jacques Tremblay demonstrated that expression of specific meganucleases in the muscle of a DMD mouse model can restore the normal reading frame of a mutated dystrophin gene.  More details in this week’s edition of Gene Therapy.

Friday Science Review: January 8, 2010

I am starting the new year and decade by recognizing the accomplishments of two distinguished scientists…

Two outstanding Canadian scientists were recognized for their valuable contributions to the global research community.

Dr. Andras Nagy’s innovative technique to reprogram mature body cells into stem cells – called induced pluripotent stem cells or iPS cells – was named Method of the Year by the prestigious journal Nature Methods.  Earlier in the year, Dr. Nagy was selected as one of Scientific American magazine’s top 10 – Guiding Science for Humanity.

Dr. Tony Pawson was honoured as one of ten “Nation Builders of the Decade” by the Globe and Mail.  His breakthrough research over the past decade and beyond has propelled our understanding of the intricate communication that goes on within a cell and between cells.  Dr. Pawson was also awarded the Kyoto Prize this year.

Bypassing PTEN Mutants in Cancer Cells: The discovery of a novel link between the proteins PTEN and PKR may lead to new approaches forncer treatments.  Dr. Antonis Koromilas’ research at McGill University identified that the tumour suppressor function of PTEN requires it to activate the PKR-eIF2alpha pathway, which applies an inhibitory control on protein synthesis.  In a cancer cell where PTEN is mutated, PKR also loses its ability to control protein synthesis and the cell continues growing into a tumour.  The significance of this is that they can now try to bypass the PTEN mutation and find alternate ways to activate PKR and regain control of cell growth.  The research is reported in the journal Science Signaling.

Distinguishing Sister Chromatids: In studying cell division, scientists have long desired to follow the fate of sister chromatids – the identical chromosome copies that is distributed to each cell during the process of cell division.  Researchers used the CO-FISH (chromosome orientation fluorescence in situ hybridization) technique with unidirectional probes.  When they observed the process in different cell types, they found that the chromatids segregated randomly in some cell types but not in others.  The non-randomness may be a mechanism to direct cells to be slightly different from its sister cell and is one of many layers of complexity in developing higher organisms.  The solution to this biological phenomenon by Dr. Peter Lansdorp at the BC Cancer Agency deserves the recognition in the prestigious journal Nature.

Prognostic Marker for Bone Cancer Survival: Genetic deletion mutations in a specific chromosome region called osteo3q13.31 may be predictive of a poor prognosis for osteosarcoma patients.  The copy number alteration (CNA) marker was identified in subsets (80%) of osteosarcoma patients where their bone cancers appeared to be more difficult to treat.  With this genetic marker, patients may be screened to identify candidates who should be treated more aggressively from the onset of diagnosis.  Furthermore, the osteo3q13.31 region contains 3 genes that were not previously associated with the disease and requires further investigation that may lead to additional therapeutic options.  The study was conducted by Dr. David Malkin’s team at The Hospital for Sick Children and is published in Cancer Research.

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