PhD Transfer Exam
Tuesday May 30th, 1:10 pm – Ramsay Wright Building, Rm. 432
Abdiwahab Moalim (Plotnikov lab)
“Investigating the role of focal adhesion-localized calcium sparks in the sensing of extracellular matrix mechanical properties“
The ability of cells to sense and to respond to mechanical cues in their environment such as extracellular matrix (ECM) stiffness underlies crucial physiological processes ranging from embryo development and stem cell differentiation to tissue homeostasis. This ability also plays a key role in pathological processes such as atherosclerosis and cancer metastasis. Despite their apparent biological and clinical significance, the molecular mechanisms that allow cells to probe ECM stiffness are currently elusive. I have recently begun to investigate how calcium signalling at integrin-based focal adhesions (FAs), sites of cell-ECM contract, mediates the ability of mouse embryo fibroblasts (MEFs) to sense mechanical cues. I demonstrated that FAs are centres of transient calcium oscillations and showed that the oscillations are controlled by actomyosin contractility and ECM stiffness. Through pharmacological perturbations I further showed that these oscillations are due to extracellular calcium entry through stretch-activated ion channels. I hypothesize that actomyosin forces open stretch-activated channels located within FAs in an ECM-stiffness dependent manner and that this signal is used as a readout for ECM stiffness. In my doctoral work, I plan to describe the distribution of calcium sparks in the focal adhesions of cells in a diversity of in vitro and in vivo mechanical environments, identify the particular stretch-activated channels responsible for these sparks, and elucidate other FA constituents that modulate spark behaviour. This work is anticipated to further our understanding of how cells interpret and navigate complex mechanical environments experienced by cells in both physiological conditions and disease.
Ramsay Wright is a wheelchair accessible building.