PhD position (m/f/d): Exploring the biophysics of nuclear pore‐like permeability barrier function

Job Offer from October 24, 2022

Exploring the biophysics of nuclear pore‐like permeability barrier function using microfluidics, chemical microscopy and theory

We seek to hire a PhD student interested in cellular and molecular biophysics to work with us to elucidate the barrier properties of the nuclear pore complex (NPC). The NPC is made up of nucleoporin proteins (Nups). Nups rich in phenylalanine (F) and glycine (G) repeat domains, called FG-Nups, form a condensate in the NPC’s central region, acting as a selective permeation barrier for nucleocytoplasmic transport. Although it is known that large cargo requires prior binding to a shuttling protein called a nuclear transport receptor (NTR), the precise mechanism of the selective transport is far from fully understood and difficult to study in vivo. In the first phase of this project, we have established a collaboration between the Max Planck Institute for Polymer Research (MPIP), the Institute for Molecular Biology (IMB) and the University of Texas at Austin (USA), in which we have therefore isolated the FG-Nups and NTRs and studied their solution behavior in-vitro. Specifically, we have developed measurement platforms for measuring barrier properties in living cells, molecular spectroscopy of in vitro FG-Nups condensates, rheological properties of FG-NUP condensates, and built a theory for extracting physical and chemical properties of the condensates in a ternary mixture.

In the second phase of this project, we aim to generate mechanistic understanding by tracking the chemical and constitutive responses of FG-Nup-rich condensates as a function of time and upon addition of cargo and NTR. For this, we make use of microfluidic platforms, as well as coverslip essays combined with in-situ optical spectroscopy, Raman spectroscopy and microrheology. We will interpret and generalize the results using computational modelling, identifying the role of multivalent “sticky interactions”, such as H-bonding and hydrophobic interactions, on both the equilibrium and the out-of-equilibrium behavior of the Nup- and Nup:NTR-condensates. With this information we hope to elucidate the mechanism that underpins the selective barrier properties within the nuclear pore complex.

We are looking for a motivated student with i) a background in physical chemistry, physics, biophysics or similar and ii) a motivation to work both experimentally and computationally. Experience with microscopy instrumentation and code development are strong advantages but not requirements. If you are interested in applying for this position, please send an application letter and CV via email to the following contacts at MPIP and UT Austin:

Dr. Sapun Parekh (parekh@mpip-mainz.mpg.de; sparekh@utexas.edu)

Dr. Jasper Michels (michels@mpip-mainz.mpg.de)

 

The MPIP, where the successful candidate will primarily work, is a world-renowned institute in macromolecular science and soft matter. The institute offers a highly international environment where the working language is English and the scientific and technical infrastructure is excellent. The access to resources and scientific expertise for this project provide every opportunity to development as an independent scientist. The PhD position is regulated by the Max Planck Society bylaws under the salary stipulated by the DFG.

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