Research Associate (in Protein Design and Synthetic Biology)

University of Bristol

The role

A post-doctoral position in protein design and synthetic biology is available from July 1 or as soon as possible thereafter, in the School of Chemistry at the University of Bristol.  The role of the successful applicant will be to design and characterise de novo proteins to form membrane-less organelles in cells. This is one of two posts funded by the Leverhulme Trust, and both are available for 3 years (see ACAD105192 for details of the other position).  It is part of a collaboration between the Peptide Design laboratory of Prof Dek Woolfson (Chemistry and Biochemistry, Bristol) and the Soft Matter group of Dr Jennifer McManus (Physics, Bristol).  The overall aim is to use de novo designed peptide modules to generate new proteins that undergo liquid-liquid phase separation both in vitro and in cells.

Synthetic Biology meets Soft Matter: Most compartments in biology—e.g., organelles, cells, organs—have defined membrane boundaries that allow control over the biological processes that occur within them, and the flux of materials and signals across them. However, certain subcellular processes occur within membrane-less organelles. These form due to demixing or liquid-liquid phase separation.  Some natural proteins have evolved to promote this process leading to the spontaneous formation of membrane-less organelles.  These natural proteins are often large and unstructured, and how they form these intriguing compartments is not understood.  This Leverhulme-funded project aims to develop simplified synthetic proteins to unpick the determinants of liquid-liquid phase separation by proteins.  In addition to understanding the fundamentals of the biophysical process, another aim is to build synthetic membrane-less organelles for applications in biotechnology.

What will you be doing?

This position will be based primarily in the School of Chemistry, but both postdoctoral researchers on this project will work closely together between both the Woolfson and McManus research groups. The project builds on and combines expertise in de novo protein design in the Woolfson lab (Fletcher, et al. (2012), ACS Synth Biol 1, 240; Thomas, et al. (2013), J Am Chem Soc 135, 5161; Thomson et al. (2014) Science 346, 485; Rhys, et al. (2019) J Am Chem Soc 141 8787), and expertise in soft matter and biophysics of the McManus lab (McManus et. al. (2016) Curr Opin Coll Int Sci 22, 73; James et. al (2015) Phys Chem Chem Phys 17, 5413; McManus et. al. (2007) Proc Natl Acad Sci 104, 16856).

This post in Chemistry will be responsible for the design, construction and production of synthetic proteins comprising multiple de novo modules.  These modules will be used to promote protein-protein interactions leading to condensates in cells, which will be screened for liquid-liquid phase separation using microscopic and spectroscopic measurements.  This part of the work will involve a combination of peptide and protein design and production, structural studies, and light and electron microscopy in both prokaryotic and eukaryotic cells

You should apply if

This position would suit talented researchers with an interest in peptide/protein design, synthetic biology and/or structural biology. You should have or soon expect to have a PhD in chemistry, biochemistry or a related subject. Expertise in preparing and working with peptides or proteins is essential, and experience in protein design and biophysics would be an advantage.

We welcome applications from all members of our community and are particularly encouraging those from diverse groups, such as members of the LGBT+ and BAME communities, to join us.

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