Senior Laboratory Research Scientist
Key information
Senior Laboratory Research Scientist
Contact term:
This is a full-time, 2-year fixed term position on Crick terms and conditions of employment.
OVERVIEW
The successful candidate will join the High Throughput Screening (HTS) facility at the Francis Crick Institute and will be part of a dynamic, multi-disciplinary team working to develop a Systems Chemical Biology approach to biomedical research through combination of chemoproteomics, high-content screening, reactive fragments and cutting-edge genomics in disease relevant biological systems. Resulting full matrix datasets will be interrogated using bioinformatics and machine learning technologies to accelerate the exploration of potential targets or pathways for therapeutic intervention. This is a multi-faceted project with a strongly interdisciplinary focus. The project will be co-supervised by Crick and GSK scientists and has considerable scope to evolve.
The HTS facility is one of the core technology platforms available to all researchers at the Crick and enables them to use screening techniques as part of their research. We use our experience of arrayed cell-based screening techniques, high content imaging and data analysis to conduct, among other things; genome-wide CRISPR and RNAi screens, large-scale cell-based screens with collections of well-characterised small molecules or proof-of-concept drug discovery screens and the development of novel screening platforms as required by researchers. For example, our recent development of a high throughput, live virus, neutralisation assay for SARS-CoV-2 which measures the ability of patient serum to prevent infection by variants of concern has been deployed to great effect and has now been spun off as a separate unit within the Crick. This current project will have a strong focus on high content phenotypic screening.
PROJECT SUMMARY
This role offers the opportunity to be part of a Crick–GSK Biomedical LinkLabs project funded by an EPSRC Prosperity Partnership award that brings together multiple research groups at the Crick and GSK to pioneer the use of reactive fragments and high-content screening technologies in cellular disease model systems).
Working in the HTS team, you will collaborate with project researchers from academia and Pharma to create, plan and conduct many high content screens using Cell Painting technologies as a way of characterising phenotypic responses to small molecules. You will have the opportunity to apply AI/ML approaches to image and data analysis and assist in the integration of this data with relevant data from other modalities.
This is an opportunity to use your accumulated biology knowledge, your skills at the bench and desire to try new things to create the most informative and valuable research data possible. You will work with highly experienced colleagues in an integrated academia–industry setting, honing the skills required by the next generation of science leaders.
KEY RESPONSIBILITIES
These include but not limited to;
Creating and perfecting bespoke assays that provide the project with reliable and interpretable data
Defining and optimising Cell Painting techniques such that they can be applied to enable the high content profiling of reactive fragment molecule activities
Engaging with the high content data output and analysis and ensuring dissemination to all project stakeholders
Work closely with Crick and GSK researchers (e.g.chemistry, high-content screening, biology, data and machine learning) to guide experimental design and drive the interpretation of outcomes.
Analyse, assimilate, and communicate complex scientific data clearly and concisely to members of the team and the broader scientific community.
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
Extensive direct experience in using cell-based assays, tissue culture and immunofluorescence-staining techniques
Previous direct experience of HTS campaigns in either Pharma or academia preferably using arrayed small molecule reagents, CRISPR or RNAi would be extremely advantageous
Experience with high throughput screening techniques and associated machinery particularly automated microscope and High Content Analysis would be extremely advantageous
Capable of self-teaching, innovating and problem solving
Self-motivated with the ability to work both independently and as part of a team
Excellent organisation and communication skills
Desirable:
Familiarity with a wide range of research techniques and biological systems
Post-doctoral research experience or extensive relevant experience in Pharma a distinct advantage
Previous experience with fragment and small molecule screening would be advantageous
Experience of analysing large biological datasets to support biomedical sciences, in particular from high content imaging.
Demonstrable organisational skills and attention to detail, with the ability to prioritise own workload.
Excellent inter-personal skills and a willingness to learn new skills and teach these to others
References
1. Bray, et al. Cell Painting, a high-content image-based assay for morphological profiling using multiplexed fluorescent dyes. Nature Protocols. 2016;11(9):1757-74.
2. Wu, et al. Three-dose vaccination elicits neutralising antibodies against omicron. Lancet. 2022.
3. Wall, et al. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. The Lancet. 2021.
4. Backus, et al. Proteome-wide covalent ligand discovery in native biological systems. Nature. 2016;534:570-574.
5. Vinogradova, et al. An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020;184:1009-1026.