This is a full-time, fixed term (4 year) position on Crick terms and conditions of employment.
The research group
The Francis Crick Institute’s Genome Function Laboratory led by Greg Findlay investigates how mutations lead to phenotypes by developing new functional genomics methods. The mission of the lab is to use powerful genome editing tools to systematically explore mutational landscapes. Our assays and integrated analyses of human genetic variation aim to reveal the molecular mechanisms underlying sequence-function relationships and to produce insights that improve rare variant interpretation clinically.
Studies of how genetic variants alter processes such as gene regulation, RNA splicing, and protein function have been historically hindered by limited means of engineering mutations in human cells. Now, with CRISPR technologies, we have unprecedented opportunity to characterize human variants experimentally. Our lab strives to accelerate such efforts by developing high-throughput approaches that scale to the large numbers of variants seen clinically. By way of example, we are performing saturation genome editing to introduce all possible variants across several key tumour suppressor genes to study each variant’s precise effect on gene function. As we have demonstrated for genes such as BRCA1, the data we produce can provide key evidence for accurately identifying individuals and families at high risk of cancer.
For more information, please visit: https://www.crick.ac.uk/research/labs/greg-findlay
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.
This post-doctoral fellowship will be funded by the Francis Crick Institute and will involve developing high-throughput functional assays using genome editing. The work will build upon methods such as Saturation Genome Editing (Findlay, Boyle et al. 2014, Nature; Findlay et al. 2018, Nature) and CRISPR/Cas9 guide RNA screening (Gasperini, Findlay et al. 2017, AJHG) to study human genetic variation at scale. Together, we will develop new assays that maximize the amount of functional data obtained per experiment.
Within this context, there is considerable flexibility for the candidate to propose a line of study with respect to biological systems and genomic regions of interest. Potential opportunities include but are not limited to:
- Developing multiplex assays to explore genotype-phenotype relationships in genes harbouring clinical variants of uncertain significance (VUS)
- Studying the sequence determinants of splicing outcomes
- Studying how rare variants alter function of regulatory elements or non-coding RNAs in normal development and cancer
- Developing single-cell sequencing readouts of variant effect
- Developing methods to systematically characterise epistatic interactions
Candidates primarily interested in data analysis are highly encouraged to apply, and will have opportunities to develop computational tools to:
- Optimise experimental design based on large-scale genotype-phenotype collections (e.g. UK Biobank)
- Optimise variant effect scoring and clinical data integration for several assays
- Build predictive models of mechanism from the lab’s experimental data
Key experience and competencies
We are looking for a curious, imaginative, and motivated scientist who has earned a PhD in molecular biology, genomics, bioinformatics, statistics, bioengineering, or a related area of research. Candidates from both experimental and computational backgrounds will be considered. Experience analysing genetics/genomics data or other large experimental data sets is required. Some experience in standard molecular biology methods is also required, though specific experience with genome editing techniques and cell culture is not necessary. It is essential that the chosen candidate have good communication skills and be able to collaborate effectively. The selected candidate will have demonstrated the ability to lead projects to completion.
Interested candidates should clearly state why they are eager to pursue this specific position in their application materials and be prepared to discuss what they’re interested in working on if chosen for interview. The successful candidate will become an integral part of our lab and be well supported by the Crick’s scientific technology platforms (STPs). Postdoctoral Training Fellows are expected to lead their own projects, collaborate, and assist in training new lab members in areas of expertise.
The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:
- PhD in molecular biology, genetics/genomics, bioinformatics, bioengineering, or a related field (or be close to PhD program completion)
- Extensive knowledge of genetics/genomics and quantitative data analysis
- Working knowledge of molecular biology incl. PCR, cloning, DNA sequencing, and familiarity with basic bioinformatics tools
- Successful record of leading projects as evidenced by publications, submitted manuscripts, preprints or available software
- Ability to clearly communicate science (motivations, methods, results, etc.)
- Ability to work efficiently, both independently and with others
- Experience in next-generation sequencing methods, single-cell genomics methods, genome editing, or multiplex assays
- Experience writing scripts, processing next-generation sequencing data, assembling analysis pipelines
- Familiarity with cell culture techniques, such as performing genome editing on cell lines and/or working with stem cells or other in vitro disease models
- History of presenting research at scientific meetings, sharing expertise with the broader field, and/or serving as an academic mentor (formally or informally)