Title: Exploring the role of cortical forces on centrosome clustering
Centrosome amplification (CA) is a hallmark of cancer characterized by the presence of extra centrosomes in a cell. Centrosomes nucleate microtubules (MTs), allowing the formation of the mitotic spindle and progression through cell division. When extra centrosomes are present, additional spindle poles cluster to form a bipolar spindle, allowing the cell to undergo a bipolar division. Bipolar divisions following centrosome clustering result in segregation errors leading to tumor heterogeneity and drug resistance. Alternatively, multipolar divisions result in highly aneuploid and likely unviable daughter cells. As such, preventing centrosome clustering to promote multipolar divisions is a promising targeted therapy for cancers with a high prevalence of CA.
The molecular mechanisms that contribute to centrosome clustering are not fully understood, and key regulators are still being explored. One such regulator is the molecular motor dynein and associated crosslinker nuclear mitotic apparatus protein (NuMA). However, the importance of these proteins in centrosome clustering has strictly been associated with their functions at spindle poles, namely spindle formation and spindle pole focusing. What has been overlooked thus far is the role of cortical NuMA/dynein in centrosome clustering. I will explore the role of cortical pulling forces on centrosome clustering in cells with CA.
I am a third year PhD student in the Bioinformatics and Computational Biology program. I work with both Dr. Sarah Olson and Dr. Amity Manning to study the dynamics of mitosis in cancer cells. This presentation is my qualifying exam for PhD candidacy.