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Biology Seminar Series

February 25, 2022 at 2:30 PM to 3:30 AM

Location:Zoom Link
Cost:Free

Please join as Dr. Zahra Kabiri, a professor at Duke University School of Medicine, holds the following seminar:

Identifying the intensity-specific modifiers of RAS signaling

The mammalian family of Ras small GTPases, composed of HRAS, NRAS, and KRAS, is mutated in one third of all human cancers. Of the three, KRAS is mutated the most often, suggesting that some features of this gene render it more likely to initiate tumorigenesis. Our group previously linked the high frequency of KRAS mutation to a bias of rare codons and the resulting poor translation of the encoded mRNA. This finding suggests that a low rather than high KRAS protein level induces tumor initiation, altering our thinking about the role of oncogenic RAS signaling intensity in cancer. Although numerous mediators of RAS pathway have been discovered, we still do not understand the processes through which the signaling intensity of this pathway is modulated.

We employed the novel approach of altering codon usage in the Ras gene of Drosophila to produce high versus low RAS signaling and exploited these two genetic backgrounds to undertake the first-ever intensity-specific modifier screen. Fifteen deficiencies were identified, of which the first we explored was mapped to the Ribosomal protein S21 (RpS21) gene. As the screen is a treasure trove of novel modifiers of RAS signaling, we plan to map the genes in the remaining deficiencies and elucidate their roles in tumorigenesis using cross-species approaches.

Identifying novel intensity-specific modifiers of RAS signaling could potentially open the door to a whole new class of cancer regulators especially in the context of drug resistance.

The seminar will be held via ZOOM on Friday, February 25th at 2:30 pm.

Please contact biology@carleton.ca to be added to the seminar emailing list.