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Tag Archives: axons

Friday Science Review: April 30, 2010

Maybe these primary research projects will lead to the next great “Dendreon” story…

Mirror-rorriM Movement Disorder: Defects in the proper connections between the left and right sides of the brain can lead to involuntary movements where one side of the body follows or mirrors the movement of the other side.  A study of two families affected by inherited cases of mirror movements led to the identification of mutations in the DCC gene (Deleted in Colorectal Carcinoma).  DCC is a receptor for netrin-1, which is a factor that is important for guiding neural axons across the midline to make the proper left-right connections.  This is a key finding in understanding the complexities of how our brains are wired.  Dr. Guy Rouleau (Université de Montréal) and Dr. Frédéric Charron (Institut de recherches cliniques de Montréal) collaborated on the study and is published in the prestigious Science journal.

Improving RNA Therapeutics: RNA interference based therapeutics is gaining traction in the biotech world (eg. Tekmira, Alnylam, MDRNA).  Enhancing the potency of siRNA is the focus of this research study published in Nucleic Acids Research journal.  The technology uses a combination of DNA and RNA analogs to increase the stability of the siRNA agent against nucleases and helps them to evade immune responses that often limit their effectiveness.  Dr. Masad Damha led his group at McGill University.

Also in Montreal, Drs. François Major and Gerardo Ferbeyre (Université de Montréal) announced the launch of the first ribonucleic acid (RNA) engineering laboratory in Canada.  They are using bioinformatics and biochemistry to come up with designer microRNAs that can control the behaviour of RNAs to control or cure cancers.

New Tumour Suppressor:  A recent study demonstrates the tumour suppressor properties of the Cdh11 gene.  The first hint of this function arose from studies showing a frequent loss Cdh11 in retinoblastoma cancers.  Using a series of animal models to determine the role of Cdh11, Dr. Brenda Gallie’s team (Ontario Cancer Institute) demonstrated the tumour suppressor properties of Cdh11 through a mechanism promoting cell death or apoptosis.  The full text article appears online in PLoS Genetics.

Lung Cancer Drug Target: CXCR4 may be the next therapeutic target for treating lung cancer.  Its overexpression in about 10% of lung cancers is associated with poor patient outcome (2.7 vs. 6.1 months survival), likely due to CXCR4’s support for the rapid growth and metastasis of tumours.  On the brighter side, anti-CXCR4 drugs, which are already in existence for the treatment of HIV/AIDS, may be “fast tracked” for testing in lung cancer patients.  Dr. Gwyn Bebb, from the University of Calgary, presented her data recently at the 2nd European Lung Cancer Conference.

Friday Science Review: April 9, 2010

New fixes for diabetes, HIV, and nerve damage…

Nano-Vaccine Cures Diabetes: To prevent the immune system from attacking pancreatic cells in Type 1 diabetes, a nanotechnology based “vaccine” was used successfully to stop the disease in mice.  The strategy involves nanoparticles that are coated with diabetes specific peptides and bound to MHC molecules. When injected into the body, they stimulate regulatory T cells – the “friendly” T cells that prevent the “bad” T cells from destroying the insulin producing beta cells in the pancreas.  The advantage of this method is that it is specific to the ‘diabetes T cells’ and there are no negative effects on the rest of the immune system.  Other autoimmune diseases may also benefit from a nanoparticle vaccine approach.  Dr. Pere Santamaria’s team at the University of Calgary describes their work in the online edition of Immunity and has licensed this innovative technology to Parvus Therapeutics, Inc., a U of C spin-off company.

Allowing Neural Regeneration: The p75NTR receptor is important for the development of the nervous system during childhood.  A new research study published in Nature Neuroscience describes an inhibitory effect of p75 neurotrophin receptors (p75NTR) in the adult nervous system.  Not only does it prevent adult nerve cells from regenerating, it actively destroys axons as necessary if any aberrant connections try to form.  This monitoring system is likely skewed in neurological diseases or disorders.  Thus, further molecular information surrounding p75NTR in the nervous system can lead to developing strategies to facilitate nerve regeneration to occur or prevent degenerative disorders.  Dr. Freda Miller and her team conducted the research at The Hospital for Sick Children in Toronto.

HIV’s Secret Weapon Revealed: The discovery of how the viral protein called Vpu facilitates HIV-1 proliferation in a host may present opportunities to block this pathway with a small molecule inhibitor.  Vpu binds to and blocks Tetherin, a natural antiviral protein on the cell surface that can sense and capture the virus and prevent production and further transmission of HIV-1.  HIV-1 has evolved with Vpu as its weapon to impede Tetherin from reaching the cell surface where it acts to tether viruses.  Now it is time for scientists to outsmart the virus and find a method to block Vpu.  Dr. Éric A. Cohen directed his team at the Institut de Recherches Cliniques de Montréal and reports the study in this week’s PLoS Pathogens journal.

Cell-Cell Krazy Glue: The integrity of cell-cell contacts is important for the maintenance of the epithelial cell layer and aberrations may contribute to disease progression such as in cancer metastasis.   Two proteins involved in this cell-cell adhesion are p120 catenin and E-cadherin.  Dr. Mitsuhiko Ikura at the Ontario Cancer Institute performed NMR structural studies to provide a detailed map and understanding of the protein-protein interaction between catenin and cadherin.  The detailed study, published in the journal Cell, describe both dynamic and static interactions that contribute to the stability of the adhesion interaction between cells.

Bring out the Bazooka: Following the article above on the epithelial cell layer, this study examines a protein called Bazooka (Par3 in mammalian cells) in fruit flies.  It is expressed on epithelial cells and acts a protein interaction hub to regulate the integrity of the epithelial structure.  Using a series of gene mutants, gene mapping and bioinformatics techniques, researchers identified up to 17 genes that associate with Bazooka to regulate epithelial structure, many of these are novel interactions with Bazooka.  Further study is necessary to determine how they work together and how this translates to human tissues.  The list of genes is available in the article online in PLoS One journal and was reported by lead researcher Dr. Tony Harris at the University of Toronto.

Friday Science Review: December 11, 2009

WOW!  A busy week in the bioscience world…

Pull Down Your ‘SOCS’ and Grow Some Nerves: A long standing question is how to get mature neurons, which stop growing at around the age of two, to start growing again after sustaining nerve damage.  The answer may lie in a protein called SOCS3 (suppressor of cytokine signaling 3).  SOCS3 controls neuronal growth in adults but when it is absent (in a knockout mouse model), axons can regenerate after nerve injury.  This process may be enhanced by supplying a cocktail of neurotrophic growth factors that the researchers also identified in their study.  This is a very important discovery that will push regenerative medicine to new therapeutic strategies.  Dr. Patrice Smith started the research as a postdoctoral fellow at Harvard University and now runs her own lab at Carleton University.  The study is published in the latest edition of Neuron.  There is also an inspirational story about Dr. Smith in the Globe and Mail.

Protecting your Brain after a Stroke: Following a stroke, neurons are at risk of permanent damage caused by overactivation of NMDARs (N-methyl-D-aspartate glutamate receptors).  A key molecular step leading to this excitotoxic neuronal death was discovered in this recent study.  The trauma causes degradation of Insig-1 (insulin-induced gene-1), which triggers the activation of the transcription factor SREBP-1 (sterol regulatory element binding protein-1).  However, when they blocked the activation of SREBP-1 they were successful in reducing the neuronal damage.  This is a promising target for generating therapeutic drugs aimed at minimizing the detrimental effects of strokes and brain trauma.  The research team was guided by Dr. Yu Tian Wang at the University of British Columbia and the study is reported in the latest Nature Medicine.

Breakthrough in Children’s Brain Cancer Research: A rare pediatric brain tumour called Central Nervous System-Primitive Neuroectodermal Tumours (CNS-PNET) offers a very poor prognosis for young patients.  In this gene expression study, a cluster of microRNAs called C19MC was found to be amplified in the diseased tissue in about 25% of the patients. This cluster acts as an oncogene that enhances cell growth and affects differentiation of neural stem cells.   The new discovery will advance opportunities to study this rare pediatric cancer and possibly use C19MC as a diagnostic marker and/or therapeutic target.  The international study was led by Dr. Annie Huang at SickKids Hospital and is reported in the current issue of Cancer Cell.

Genomics Study on Pathogenic Factors: In a large scale study of bacterial genomes, it was proven broadly across microbial species that many of the bacterial virulence factors are contained within genomic islands or clusters of genes.  The virulence factors are proteins that have more “offensive” functions such as toxins that help the bacteria invade the host.  Another significant outcome of this research is the discovery of potentially new pathogen-associated genes that are present pre-dominantly in pathogenic bacteria but less frequently in the non-pathogenic bacteria.  These factors require a closer look as they may represent novel targets for anti-microbial drug development, a critical area of research to combat the increasing prevalence of drug resistant bacteria.   Dr. Fiona Brinkman’s team at Simon Fraser University conducted the research and is detailed in PLoS One.

Dabigatran vs. Warfarin (round 2): Following up on a study that I mentioned here earlier this year, new research further supports the use of Dabigatran over Warfarin.  Patients with a common clotting disorder called venous thromboembolism (VTE) can benefit from Dabigatran as an equally effective and safe blood thinning treatment but without the complications associated with using Warfarin, which requires frequent visits to the clinic for blood monitoring and dosage adjustments.  The study was conducted by Dr. Sam Schulman at McMaster University and appears in this week’s The New England Journal of Medicine.

Research on Congenital Myopathy in Mice:  University of Toronto scientists have generated a mouse model to study a specific type of skeletal muscle disorder.  The mice express a mutant form of the RyR1 protein (type 1 ryanodine receptor/Ca2+ release channel), which causes a severe form of central core disease (CCD). Symptoms in mice that mimic the human condition include progressive congenital myopathy, respiratory stress, skeletal muscle weakness and impaired mobility.  Their study offers insight and future potential to unravel the mechanism behind the disorder.  Dr. David MacLennan’s research is published in The Proceedings of the National Academy of Sciences.

Here is a list of many more important research reports this week from across the country:

Cofactor-activated phosphorylation is required for inhibition of cortical neuron differentiation by Groucho/TLE1. (Dr. Stefano Stifani, McGill University)

Dlx5 Is a cell autonomous regulator of chondrocyte hypertrophy in mice and functionally substitutes for Dlx6 during endochondral ossification. (Dr. Andrew Bendall, University of Guelph)

Pluripotent transcription factors possess distinct roles in normal versus transformed human stem cells. (Dr. Mickie Bhatia, McMaster University)

Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo. (Dr. Tak Mak, The Campbell Family Institute for Breast Cancer Research and University of Toronto).

A novel enediynyl peptide inhibitor of furin that blocks processing of proPDGF-A, B and proVEGF-C. (Dr. Amik Basak, University of Ottawa)

The specificity of the FOXL2 c.402C>G Somatic mutation: a survey of solid tumors. (Dr. David Huntsman, University of British Columbia)

Nuclear function of Smad7 promotes myogenesis. (Dr. John McDermott, York University)

Asf1-like structure of the conserved Yaf9 YEATS domain and role in H2A.Z deposition and acetylation. (Dr. Michael Kobor, University of British Columbia)

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