The Francis Crick Institute

Laboratory Research Scientist – Balchin lab

The Francis Crick Institute

London, United Kingdom

Laboratory Research Scientist – Balchin lab

Reports to: David Balchin, Group Leader

This is a full-time, fixed term (6 months) position on Crick terms and conditions of employment, which could also be offered as a secondment.

Summary

This position is for a fixed-term Laboratory Research Scientist (LRS) in the Balchin Laboratory led by David Balchin. The postholder will provide support to a laboratory that seeks to understand molecular mechanisms of protein biogenesis. In addition to general tasks in organising the laboratory infrastructure, the LRS is expected to implement biochemistry and molecular biology workflows in the laboratory, including the optimisation of recombinant protein production and reconstituted protein synthesis reactions. Suitable candidates should have a strong background in molecular and cell biology, biochemistry or related fields.

Project summary

Proteins are synthesised on the ribosome as linear polypeptides that in most cases must fold into defined 3-D structures to be biologically active. How this occurs is a fundamental problem in biology. Although few proteins fold efficiently in a test tube, in vitro studies of isolated model proteins underpin our current understanding of the folding process. Folding in vivo is a much more sophisticated operation. Cells employ a complex network of protein biogenesis factors that stimulate folding reactions, reverse misfolding, and inhibit aggregation. Failure of the cellular protein folding machinery has severe consequences. Protein misfolding is a hallmark of neurodegenerative disease, cystic fibrosis and type II diabetes, and a key contributor to the process of aging.

The overarching goal of our lab is to understand protein biogenesis in molecular detail. To do this, we take a bottom-up approach. We reconstitute intricate cellular protein synthesis and folding networks in vitro using purified components, and apply a range of biochemical, biophysical and structural approaches to characterize dynamic folding intermediates. By bridging the gap between in vitro and in vivo concepts of protein folding, we also hope to understand the molecular principles underlying protein misfolding diseases in humans.

Initial work will focus on the coordination between protein folding and synthesis at the ribosome. “Co-translational” folding is the first step in the biogenesis of all proteins in the cell, and can have a profound influence on protein structure and function. To determine the underlying mechanisms, we are developing new ways to follow the folding of nascent proteins on the ribosome, using hydrogen/deuterium exchange-mass spectrometry, crosslinking-MS, FRET, and cryo-EM.

Key responsibilities

These include but are not limited to:

  • Management of lab, instruments and supplies on a daily basis
  • Cloning, site-directed mutagenesis and expression of proteins in coli
  • Establishing workflows for reconstituted protein synthesis reactions
  • Training new lab members in SOPs
  • Encouragement of a positive, motivating lab atmosphere

Key experience and competencies

The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:

Essential

Qualifications, experience and competencies:

  • Higher education degree in biochemistry, molecular biology or similar
  • Experience in molecular biology (cloning, recombinant protein production) and protein biochemistry (e.g. Western blots)
  • Experience in preparation and in vitro analysis of E. coli translation factors, including ribosomes
  • Strong skills in organising and thorough record-keeping
  • Strong collaborative ability and teamwork experience

Desirable

Qualifications, experience and competencies:

  • Experience in structural/biophysical analyses of proteins

Please apply via recruiter’s website.