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DTSTART;TZID=UTC:20260331T100000
DTEND;TZID=UTC:20260331T110000
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SUMMARY:PhD Qualifying Exam
DESCRIPTION:Examinee:\nShelly Anne GNAPRAGASAN\, Michelot Group\n \nTitle: \nEFFECT OF ACTB MUTATION ON ACTIN CYTOSKELETAL STRUCTURE AND DYNAMICS\n \nAbstract:\nBaraitser Winter syndrome 1 (BWS1) is a rare congenital disorder caused by heterozygous mutations in the ACTB gene. ACTB encodes β-actin\, a major cytoplasmic actin isoform that is essential for cytoskeletal organization and regulates key cellular processes\, including cell morphology\, migration\, and immune cell function. Patients with BWS1 frequently present with immune dysfunction and recurrent infections\, indicating a critical requirement for β-actin in immune cell activity. However\, the molecular mechanisms by whichACTB mutations impair actin function and compromise immune responses are not understood. I hypothesize that patient derivedACTB mutations alter β-actin structural integrity and biochemical properties\, leading to defects in cytoskeletal organization and downstream immune cell dysfunction. To investigate this\, I will use the highly conserved and genetically tractable yeast (Saccharomyces cerevisiae)  actin homolog\, ACT1\, as a model system to study BWS1 associated mutation G366V. Using haploid yeast strains expressing mutant actin\, I will quantify actin expression level and characterize growth defects of mutant cells. I will examine F-actin organization and dynamics using actin markers in order to determine which actin networks and functions are affected by this mutation. In parallel\, I will perform in depth structural analysis of this mutation to formulate hypothesis about its biochemical consequences. I will purify this actin mutant to characterize its stability\, polymerization defects\, and potential altered interactions with actin-binding proteins (ABPs). To establish translational relevance\, findings from yeast will be extended to immune cells (cytotoxic T cell) through collaboration to determine how actin dysfunction contributes to impaired immunological synapse (IS) formation critical for immune cell function to fight infection. Overall\, this multiscale approach will provide mechanistic insights caused by ACTB mutations and may reveal critical regulatory pathways that can be targeted to restore cytoskeletal function and improve immune cell activity in BWS1 patients.\n \nImportant Note\nThe examination following the seminar is a closed-door session. All attendees are requested to exit from the meeting room after student’s presentation/Q&A.
URL:https://mbi.closelycoded.site/event/phd-qualifying-exam/
LOCATION:T-Lab Level 5 Seminar Room
CATEGORIES:PhD Qualifying Exam
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