研究领域

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Dr. Grierson's research focus is on discovery and development using small molecule library synthesis of biologically active molecules with application in cancer, HIV/AIDS, cardiovascular disease and genetic disorders. Current research projects include: A new approach to treating HIV/AIDS infection: Alternative Splicing Inhibitors Problems of drug compliance, drug resistance and toxic side effects limit the effectiveness of the combination therapy (HAART) approach to treating HIV/AIDS in the long term. There is thus a constant need for new drugs and in particular those acting through new, and as yet unexplored mechanisms. In collaboration with Pr. Jamal Tazi (U. Montpellier II, France) and Dr. Florence Mahuteau-Betzer (Institut Curie, Orsay, France) the lab is developing inhibitors of specific alternative splicing events which are vital to the production of the critical HIV proteins Tat, Rev, Vpr, Vpu and Nef. In particular, Tat plays a key role in virus multiplication, and inhibition of Tat function may provide a means to attack the latent HIV resevoir, thereby irradicating HIV infection. Our lead compound IDC16, identified by small molecule library screening, interfers with the exonic splicing enhancer activity of the splicing factor SF2/ASF, thereby blocking Tat synthesis and assembly of infectious particles. Following on this discovery, the lab is engaged in the synthesis and development of a new drug for the treatment of HIV/AIDS. This research is novel in that such a drug will target the host cell machinery, rather than a viral proteins which are subject to constant mutation. Development of Arginine Methyl Transferase inhibitors Protein Arginine N-Methyltransferases (PRMTs) are eukaryotic enzymes that transfer one or two methyl groups from S-adenosyl-L-methionine (AdoMet) to the terminal nitrogen atoms on arginyl residues within protein substrates, thus producing mono- and/or dimethylarginyl residues and S-adenosyl-L-homocysteine (AdoHcy). This post-translational modification regulates a variety of cellular processes including RNA transcription and processing, and signaling pathways by modulating macromolecular interactions.In collaboration with Professor Adam Frankel (Faculty of Pharmaceutical Sciences), a programme is underway to discover specific inhibitors of PRMT6 using the "fragment" based approach.