Closing date and time:
The position will remain open until suitable candidates are found.
This is a full-time, fixed term 4 years position on Crick terms and conditions of employment.
We are seeking an experienced, talented and dedicated structural biologist to join our team as Postdoctoral Fellow. The position will be laboratory-based and will require the implementation of cryo-electron microscopy and cryo-electron tomography to study the activation mechanisms of bacterial proteolytic complexes by bacterial PROTACs and other degraders. The successful candidate will join our newly established Targeted Protein Degradation & Antibiotic Research laboratory at the Francis Crick Institute.
Our multidisciplinary research group aims to establish targeted protein degradation technology in pathogenic bacteria, integrating structural biology, chemical biology and microbiology. As a postdoc in our group, you will be part of a dynamic and collaborative team, driving your project and collaborating with other lab members with complementary expertise.
Candidates interested in this role should apply via our website and include a cover letter highlighting how their experience and skills match the job description and indicating:
their research interests and how they align with the work of our laboratory
their earliest potential start date
Please submit your application at the earliest availability, the position will remain open until suitable candidates are found. Informal enquiries can be directly addressed to firstname.lastname@example.org
Targeted degradation of bacterial proteins holds the potential of significantly expanding the number of tractable antimicrobial targets and represents a novel approach to antibiotics discovery. In bacteria, degrader molecules known as BacPROTACs function by reprogramming ClpCP proteolytic complexes, normally controlling protein quality and turnover, towards selected proteins of interest (Morreale FE et al. Cell, 2022). Beyond their degradation-inducing function, BacPROTACs are able to stabilise usually transient states of the active ClpCP complex, and induce its oligomeric rearrangement.
The aim of the current postdoc project is to study the structural basis for proteolytic complexes activation and reprogramming by BacPROTACs and other degradation-inducing molecules, visualising active ternary complexes in vitro and in bacterial cells.
The successful candidate will interact closely with structural biologists, medicinal chemists and microbiologists, and will have access to a range of in-house state-of-the art equipment and expert support for transmission electron cryomicroscopy (single particle cryo-EM, cryo-ET). This includes advice, training and instrumentation for sample preparation (negative stain and plunge freezing), cryo-grid screening (FEI 120kV microscopes and FEI 200kV Talos Arctica microscopes), data collection on the FEI Titan Krios microscopes and data analysis and processing.
Key experience and competencies
The post holder should embody and demonstrate our core Crick values: bold, open, collegial, in addition to the following:
PhD in Structural Biology or related subject
Excellent theoretical and practical expertise in structure determination through cryo-electron microscopy, including sample preparation, data collection and processing, model building
Track record of writing papers as evidenced by publications or submitted manuscripts
Ability to work independently and also to interact within a group
Enthusiasm, creativity, critical thinking and problem-solving skills
Excellent communication skills, including the ability to write for publication and present results at scientific meetings
Experience with cryo-electron tomography
Experience with structure determination of protein-ligand complexes
Experience with working in multidisciplinary research teams.
The newly established laboratory of Dr Francesca Ester Morreale focuses on enabling targeted protein degradation technology for the discovery of novel antibiotics. https://www.crick.ac.uk/research/labs/francesca-ester-morreale
At the Crick, we conduct research at the forefront of biomedical research. We combine rigour with an open and collaborative culture, and are outward-looking, reflecting our status as a partnership of six organisations aiming to pool knowledge, ideas and resources.
We have a wide research portfolio with no divisions or departments, bringing biomedical researchers together with clinicians, physical scientists and applied scientists from our pharmaceutical partners.
We aim to attract the most talented researchers and support them to tackle innovative research questions. Our science technology platforms provide our researchers with access to state-of-the-art technology and expertise.
We provide an excellent learning environment with dedicated education programmes in public engagement with science, education and personal development, and a postdoc training programme that prepares scientists for leadership roles in science.
If you are interested in applying for this role, please apply via our website.
All offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom.
If you require a visa to work in the UK we will help support your application should you be successful