Université de Montréal, Inst. for Research in Immunology & Cancer
Monday, December 10, 2018 - 3:00pm
Davenport Seminar Room, Chemistry Department, 80 St. George St.
The central dogma of molecular biology has been the transfer of genetic information from DNA, by way of an RNA intermediary, to protein. Traditionally, proteins are considered the actors in the cell, carrying out a wide variety of biochemical activities required for cell life. Cancer cells are often considered to arise because of mutations to the genome which lead to aberrant or even absent protein effectors and subsequently, dysregulated cell growth. However, things appear more complicated then these models would suggest. For instance, the RNA intermediary was initially considered a simple message, passed from the home of the DNA, the cell nucleus, to the cytoplasm, where this message was translated into protein. However, measures of the genome (the DNA content of the cell), the transcriptome (all the RNA messengers) and the proteome (all proteins in the cell) indicate large disconnects whereby the transcriptome does not always predict the proteome. This leads to the essential questions: why don’t they agree and how does this discordance arise? It seems that there must be forces and mechanism in place, a sort of genetic dark matter, to explain these observations. My laboratory has been studying the mechanisms that drive these pathways. In essence, these mechanisms modulate levels, modifications and ultimately activity to distort the message originally sent by the DNA. This can be for the good, to respond to environmental stresses but many of these mechanisms are also co-opted by cancer cells for their own nefarious purposes. We use biophysics, NMR, cell biology methods to study these processes and have identified pharmacological means to target these in cancer patients leading to several early stage clinical trials and remissions in patients. We have also identified a new form of multi-drug resistance in these cells, inducible drug glucuronidation and have used NMR based fragment screening to identify means to overcome this.
Chemistry Department Seminar