Amazing! Three Nature papers this week…
Cracking the Code: The human body is much more complex than the 20,000 or so genes that are encoded in our DNA. This multiplicity of genetic messages is enhanced by alternative gene splicing, a process where different segments of DNA exons are spliced together to create a different gene message. It is possible to create hundreds of new messages from a single gene. The so called “splicing code” or rules that determines how and where a particular part of a gene is spliced with another segment was deciphered by researchers at the University of Toronto. They can now accurately predict how genetic messages are rearranged on a large scale. Hundreds of different RNA features are taken into account including certain factors in specific tissues to give rise to tissue specific expression. This is an amazing discovery by Drs. Brendan Frey and Benjamin Blencowe that garnered the cover story in this week’s Nature journal.
Stem Cells on Hormones: The ovarian hormone, progesterone, stimulates breast stem cells as its levels peak during the natural reproductive cycle. Researchers observed up to a 14-fold expansion of breast stem cells at peak progesterone levels in a mouse model. This is the first evidence of a direct link between hormones and breast stem cells. Since cancers are thought to initiate from stem cells, if there are other oncogenic factors pushing the system this may be a critical point that ultimately drives the start of a cancer. There are implications of this study to further understanding how reproductive history is a strong risk factor for breast cancer and may lead to therapeutic intervention. The research team at Princess Margaret Hospital, University Health Network was led by Dr. Rama Khokha and describes their work in Nature.
Reversing HER2 Breast Cancer: Through genomic studies of HER2 positive breast cancer, it was noted that the 14-3-3sigma gene was frequently missing. After several years of hard work focusing on this gene, researchers have demonstrated that the 14-3-3sigma gene does indeed play a specific role in the development and function of breast epithelial tissue. In the absence of 14-3-3sigma, the normally organized and polarized sheets of epithelial cells clump together and lose polarity. It is this loss of organization without 14-3-3sigma that likely contributes to breast cancer progression. From a therapeutic standpoint, the reintroduction of 14-3-3sigma into HER2 positive breast cancer cells resulted in the restoration of cell polarity and opens a window for further studies as a pathway to target. Dr. William Muller (my former mentor) and his team at McGill University describe their research in the early edition of Genes and Development.
Bionic Muscle: Artificial proteins were assembled together in a fashion that mimics the molecular spring structure of a muscle protein called Titin, which is a very large protein that gives muscle tissue its unique properties of strength, extensibility and resilience. This is why muscle has superior elasticity. The biomaterial looks like a string of beads and although it exhibits only some of the mechanical characteristics of muscle tissue, its structure can be adjusted to provide specific properties of different types of muscle. There are obvious future applications of this technology in regenerative medicine and tissue engineering. Drs. Hongbin Li and John Gosline at the University of British Columbia present their work in this week’s Nature journal.
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.