April 23, 2010
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Iron Man 2: Actually, this is about IRP2 – Iron Regulatory Protein 2. Ok, not quite as exciting as the superhero movie but it is interesting/unexpected that overexpression of IRP2 promotes cancer cell growth. In contrast, the very similar IRP1 protein suppresses tumour growth. The difference seems to lie within a 73 amino acid sequence in IRP2 that is required for its growth promoting properties. It is a long stretch to try to make any link between iron intake and cancer based on this preliminary study but it does warrant further research to understand the roles of IRP1 and IRP2. Dr. Kostas Pantopoulos (McGill University) published his study in PLoS One.
Not All Herpes are the Same: There are many different strains of herpes viruses, each with slightly different properties and responses to drugs. Human herpesvirus 6A and 6B (HHV-6A, HHV-6B) variants are prime examples of this. Classic anti-viral drugs based on type 1 Interferon (IFN) are effective against HHV-6A infected cells but not cells infected with HHV-6B. Dr. Louis Flamand’s group at Université Laval’s Centre de Recherche en Rhumatologie et Immunologie (CRRI) worked out some of the molecular details explaining this difference. They mapped a 41 amino acid region in the IE1 protein that is present only in the HHV-6B strain, which acts to block any further genetic responses to the IFN drugs. These small differences between herpes strains make it difficult to effectively treat infected patients but research such as this one are very important to identify how to better target each specific strain. The study is reported in this week’s issue of the Proceedings of the National Academy of Sciences.
Hippos are Your (Kidney’s) Friend: Polycystic Kidney Disease (PKD) is a common genetic disease affecting an estimated 12.5 million people worldwide and is the forth leading cause of kidney failure. Researchers are unraveling the key molecular players involved in PKD. In this study, Dr. Liliana Attisano’s team (University of Toronto) took a closer look at the Hippo pathway and identified a new function for the transcriptional activator, TAZ. TAZ modulates the beta-Catenin/Wnt signalling pathway, which is important in development and morphogenetic events. Mouse knockouts that do not express TAZ develop polycystic kidneys and demonstrate the role that these pathways play in kidney disease. This study is reported in the latest edition of Developmental Cell.
Ovarian Cancer Cells Avoid Death: Researchers studying ovarian cancer determined the mechanism by which ovarian cancer cells thrive. The sequence goes like this: ovarian cancer ascites triggers an adhesion protein called alphavbeta5 integrin; this activates FAK phosphorylation and correlates with Akt activation; the Akt pathway inhibits the molecular events leading to cell death or apoptosis. Thus, ovarian ascites confers protection against cell death. This study reveals some possible key target points for therapeutic intervention in the treatment of ovarian cancer. Dr. Alain Piche at the Université de Sherbrooke describes his work in the journal Oncogene.
April 9, 2010
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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.