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Ankita Jha

National Institutes of Health

I am a cell and developmental biologist currently working as a post-doctoral research fellow in Clare Waterman’s group at National Institutes of Health, Bethesda USA. I am interested in the spatial organization and patterning of signaling components on the plasma membrane and how signaling dynamics regulate downstream cytoskeletal processes. I am currently looking at the bleb-based migration under low adhesion and high confinement in melanoma metastatic cells. I am curious about how metastatic cells remain polarized while moving under different extra-cellular matrix conditions?

During my PhD, I worked under the mentorship of Thomas Lecuit in Marseille France and in collaboration with Satyajit Mayor in NCBS, Bangalore India to work on the interface of membrane organization of signaling components on the plasma membrane regulating mechanics during gastrulation. I was curious to understand molecular basis of germ-band extension, which is one of the key morphogenetic events during gastrulation. To understand this, I did quantitative measurements of receptor-ligand interactions on the plasma membrane by using fluorescence correlation spectroscopy (FCS) and reported activation of receptor by measuring receptor cluster formation in vivo. I also reported the importance of de-sensitization pathway and endocytosis on receptor signaling from the plasma membrane. I proposed a mechanism of dynamic modulation and arrangement of receptors on the membrane regulating quantitative Rho-Rok signaling during cell shape changes in gastrulation.

Ankita Jha has commented 1 time

1 month

Ankita Jha

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Thank you for your summary and great suggestions.
One of the most exciting findings of this work for us is the discovery that even short-term activation of an oncogene (only 5 hours) affects how cells control their shape during mitosis. Understanding the molecular mechanism behind these changes is one of our key aims in following up this study. We think it is likely to involve multiple Ras-induced changes to downstream signaling pathways, cell morphology and actin organization in interphase and during mitotic rounding. Ras-induced alterations to Cdk1 activation during mitotic entry may play a part in these changes, as you suggest. We will certainly include this hypothesis in our investigations.

We find that Ras-expressing cells are softer than controls in interphase and therefore increase their stiffness more when they enter mitosis. This allows them to round up better under confinement. We do not yet understand how Ras functions to alter cell mechanics, but this is something we plan to address in our future work. Your suggested experiment of using STORM imaging to measure cortical thickness is a great one – it would be interesting to know whether Ras alters intrinsic features of the cortex such as thickness or actin filament organization and how this differs between interphase and mitosis. It would also be very interesting to study these effects in different contexts – for example, while single rounded cells soften following Ras activation, cells in an epithelium have been shown to stiffen (Gulleckson et al 2017).

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