physical cell biology of neurodegeneration

We seek motivated applicants to apply cell biology, mechanobiology and biophysical approaches to study the initiation of neurodegeneration.

The misfolding and aggregation of proteins during aging causes neurodegeneration. Recently, it was observed that some neurotoxic proteins condense into viscous liquid droplets in the cell (a process known as phase separation), which have been proposed to be both intermediates on the path to toxic amyloid aggregates, and toxic agents per se. However, it remains unclear how these phase transitions are initiated during aging. The physical characteristics of neurons change during aging, for example they become dehydrated, lose the ability to efficiently degrade proteins or become compressed. These changes may perturb the intracellular environment. Using new tools, including a gene that enables cells to produce a steady supply of fluorescent nanoparticles that act as tell-tales for shifts in intracellular physical properties [1], we will study the initiation of phase separation and aggregation in cellular and organoid models of neurodegeneration. Experience in neuronal cell biology, quantitative microscopy, mechanobiology or biophysical analysis are beneficial, but we also aim to provide an environment that enables professional development and the acquisition of new skills.

Note: the above is a general guide, we develop project ideas in close  collaboration with postdoctoral researchers to find the best and most exciting match the interests of the lab and the individual.

Interested parties should send a CV and a one page cover-letter that briefly describes a project idea to Liam Holt:

Liam.Holt@nyulangone.org

[1] M. Delarue, G. P. Brittingham, S. Pfeffer, I. V. Surovtsev, S. Pinglay, K. J. Kennedy, M. Schaffer, J. I. Gutierrez, D. Sang, G. Poterewicz, J. K. Chung, J. M. Plitzko, J. T. Groves, C. Jacobs- Wagner, B. D. Engel, and L. J. Holt, “mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm by Tuning Crowding.,” Cell, vol. 174, no. 2, pp. 338–349.e20, Jul. 2018.