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Senior Laboratory Research Scientist at Francis Crick Institute
London, United Kingdom
Job Descrption
Reporting to: Michael Howell, Head of High Throughput Screening STP
Contract term: This is a full-time, fixed term (3 years) position on Crick terms and conditions of employment.
The Partnership
The newly funded Molecular Glue Discovery Partnership represents an exciting new research partnership between the Francis Crick Institute and Imperial College working in close collaboration with AstraZeneca, to develop systematic approaches to exploit endogenous protein degradation pathways to target un-druggable disease-relevant proteins or protein complexes. By combining fundamental biology with proteomics, high throughput screening, protein engineering and chemical biology approaches, we seek to discover and develop new molecular glues to induce degradation of proteins of interests through the ubiquitin... proteasome system or autophagy (Kozicka et al. Cell Chem Biol 2021, Słabicki et al. Nature 2020). The ultimate aim is to unlock novel biology and exploit the revolutionary therapeutic potential of glue degraders. This work is funded through an £11.2M leveraged public- industry grant and will bring together bringing together a team of 12 postdoctoral biochemists, cell, structural and chemical biologists and 3 PhD students working across 8 laboratories and scientific technology platforms (STPs) at the Francis Crick Institute with a wide range of expertise and biological interests:
Oncogene Biology - Head: Julian Downward http://shorturl.at/fhmEV
Cellular Degradation Systems - Head: Anne Schreiber http://shorturl.at/cloCT
DNA Recombination and Repair Laboratory – Head: Stephen West http://shorturl.at/HlL8e
Visual Biochemistry – Head: Radoslav Enchev http://shorturl.at/y3467
High Throughput Screening – Head: Michael Howell http://shorturl.at/dDEN4
Proteomics – Head: Mark Skehel http://shorturl.at/deHZ0
Scientific Computing: Karen Ambrose/ Amy Strange http://shorturl.at/acmoU
Chemical Biology - Head: Ed Tate http://shorturl.at/aboQ8
The High Throughput Screening STP
The High Throughput Screening (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. Activities can include, but are not restricted to; genome-wide CRISPR and RNAi screens, large-scale cell-based screens; biochemical cell-free 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 neutralisation assay to assess the ability of patient serum to prevent infection by variants of concern has now been spun off as a separate unit within the Crick (see references). In addition, we use our knowledge and technologies to automate and improve current research practises e.g. making and selecting CRISPR knockout cell lines.
PROJECT SUMMARY
We are seeking an enthusiastic SLRS researcher (ideally with postdoctoral experience) to help create, validate and execute proximity-based cell screens and cell-free assays for the identification and validation of molecular glue degraders. The large majority of intractable targets may only be correctly folded in cells where they bind to other proteins, nucleic acids, metabolites, etc. to exercise their function(s). Such targets require development of high-throughput screens in cellular or appropriate cell free reconstituted environments; in addition, molecular glue hits in primary screen are expected to be low affinity, requiring the development of sensitive cellular and cell-free screening assays.
This position will require you to collaborate with researchers to co-develop assays, plan and conduct large-scale screens balancing a number of distinct projects at different levels of development simultaneously. This is an opportunity to use your accumulated biology knowledge and curiosity about other areas of biology as well as your skills at the bench and desire to try new things towards creating the most informative and valuable research data possible. You will work with highly experienced colleagues and collaborators in an institute that values discovery without boundaries.
KEY RESPONSIBILITIES
These include but not limited to;
• Running multiple screening projects simultaneously
• in vitro and cellular assay development
• Ensuring your domain specific knowledge is sufficient to create optimal assays
• Managing workload, co-ordinating and maintaining a productive dialogue with all partnership members
• Keep up to date with the activities in the Partnership to anticipate future needs
Key experience and competencies
The post holder should embody and demonstrate our core Crick values: bold, open, and collegial, in addition to the following:
Essential
• Extensive direct experience in using and developing both cell-free and cell-based assays,
• Extensive direct experience of a range tissue culture systems. Ideally, direct experience of cell or biochemical proximity assays.
• Previous direct experience of HTS campaigns in either Pharma or academia utilising a range of screening modalities
• Demonstrable practical experience with high throughput screening techniques and associated machinery
• Able to maintain a productive dialogue with facility users and educate users in techniques and use of specific machines for high throughput screening
• Ability to quickly understand and appreciate unfamiliar areas of biology in order to create the best assay possible with users
• 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
• 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
• Previous experience of service provision preferred
Find out what benefits the Crick has to offer:
For more information on our great pay and benefits package please click here: https://www.crick.ac.uk/careers-and-study/life-at-the-crick/pay-and-benefits
Equality, Diversity & Inclusion:
We welcome applications from all backgrounds. We are committed to providing equal employment opportunities, regardless of ethnicity, nationality, gender, sexual orientation, gender identity, religion, pregnancy, age, disability, or civil partnership, marital or family status. We particularly welcome applications from people who are Minority Ethnic as they are currently underrepresented in the Crick at this level.
Diversity is essential to excellence in scientific endeavour. It increases breadth and perspective, leading to more innovation and creativity. We want the Crick to be a place where everyone feels valued and where diversity is celebrated and seen as part of the foundation for our Institute’s success.
The Crick is committed to creating equality of opportunity and promoting diversity and inclusivity. We all share in the responsibility to actively promote dignity, respect, inclusivity and equal treatment and it is our aim to ensure that these principles are reflected and implemented in all strategies, policies and practices.
Read more on our website: https://www.crick.ac.uk/careers-and-study/life-at-the-crick/equality-diversity-and-inclusion
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