A productive week of international collaborations leading to new drugs or targets…
Genetic Map of Yeast: A large-scale, genome-wide interaction map of yeast genes was constructed in an international study. The extensive network of genetic interactions lays out a functional map of the cell where similar biological processes can be grouped together. Yeast has been studied in the past and present because their molecular signaling is similar to human cells and is easy to manipulate. The detailed “genetic atlas” in this project, a first for any organism, provides important information to better understand genetic functions in relation to diseases. Their technique also allowed the scientists to map interactions between genes and chemicals, which will aid in choosing drug targets by predicting the extent of the interaction with other genes and how it may affect the cell. The multi-national project was led by University of Toronto researchers Drs. Brenda Andrews and Charles Boone. Details of the yeast map study appear in the prestigious journal, Science.
Mutations in Lymphomas: The identity of new mutations associated with specific types of lymphomas is described in this latest Nature Genetics article. Sequencing of genes involved in the NF-kappaB signalling pathway led to the identification of recurrent mutations affecting the EZH2 histone methyltransferase enzyme. The oncogene is the second member of this enzyme group found to be mutated in different types of cancer. Mutations were found in over 21% of a lymphoma subtype, affecting amino acid Tyrosine 641 that renders the enzyme with lower activity. Dr. Marco Marra at the Michael Smith Genome Sciences Centre (BC Cancer Agency) conducted the sequencing project.
Stopping Alzheimer’s Disease: Inhibition of ACAT1, an enzyme directly involved in cholesterol metabolism, significantly decreases the accumulation of amyloid plaques when tested in a mouse model of Alzheimer. To gain deeper knowledge of how this works, researchers deleted the ACAT1 gene in mice predisposed to develop Alzheimer’s disease. The brains of these mice had fewer amyloid plaques with improved cognitive function. The key finding is that without ACAT1 function, cholesterol accumulates in a subcellular compartment of the cell where it is converted and no longer available to be involved in amyloid plaque formation. These data supports the use of ACAT1 inhibitors in the battle against Alzheimer’s disease and lends insight into future improvement. Dr. Nabil Seidah at the Institut de Recherches Cliniques de Montréal collaborated with researchers in the U.S. and published the study in the Proceedings of the National Academy of Sciences.
New Treatment to Stop Malaria: Two enzymes important to the survival of Plasmodium falciparum, the parasite causing malaria, have been discovered in an international collaboration aimed at stopping the drug-resistant parasite. Malaria parasites invade red blood cells and digest the proteins for fuel to grow and divide until they burst out of the red blood cell and repeat the process again. The discovery of the parasitic enzymes, PfA-M1 and PfA-M17, which are keys to the digestive process in red blood cells, was the first step in designing therapeutic drugs. Building three-dimensional structures of the enzymes was the next step in determining how best to target and inhibit the enzyme. The study suggests that blocking PfA-M1 and Pfa-M17 would prevent the parasite from feasting on the red blood cell and represents a new wave of promising anti-malarial drugs. McGill University’s Dr. John Dalton led the international research project and is reported in this week’s The Proceedings of the National Academy of Sciences.
Vitamin D fights Crohn’s Disease: Vitamin D deficiency in individuals may contribute to the development of Crohn’s disease, as suggested in this new research report. Mismanagement of intestinal bacteria triggers an inflammatory response that develops into the autoimmune disorder. The action of Vitamin D, as the study suggests, is to directly promote the expression of NOD2, which signals to the body of a microbial invasion. NOD2 then activates NF-kappaB to induce expression of DEFB2 (defensin beta2), an anti-microbial peptide. To further support Vitamin D’s role, both DEFB2 and NOD2 have been linked to Crohn’s disease in earlier studies. This is significant to the management of the disease because Vitamin D deficiency is easy to test for through a simple blood test and Vitamin D supplements (and sunlight!) are readily available. Dr. John White and his team at McGill University and the Université de Montréal published their study in the Journal of Biological Chemistry.