PhD in Functional Nanomaterials “Enabling temporally-resolved CRISPR screening in human cells using live microscopy phenomics, single cell analysis & AI”
We are aiming to recruit an enthusiastic PhD student to help establish temporally-resolved CRISPR arrayed screening in human cells using multi-process ‘live’ reporters of cell activity (e.g. proliferation), single cell analysis and AI.
The project is joint between the Bristol Centre for Functional Nanomaterials (BCFN) at the University of Bristol in the group of Professor Rafael E Carazo Salas (https://research-information.bristol.ac.uk/en/persons/rafael-e-carazo-salas(a7638b29-53e4-49ba-82b5-98b21d82f41f).html), and AstraZeneca, a multinational pharmaceutical and biopharmaceutical company with a headquarters in Cambridge (https://www.astrazeneca.co.uk/). The work will be highly interdisciplinary, collaborative between both institutions, and benefit from the training opportunities offered by the BCFN (http://www.bristol.ac.uk/physics/functional-nanomaterials/).
Rationale:
Endpoint high-throughput microscopy screening using conventional (supervised) image analysis provides limited “static” phenotypic information from cells. Temporally-resolved screening provides richer “dynamical" phenotypic signatures of cells. Leveraging that temporally-resolved information with Deep Learning/AI could allow much more sensitive and precise hit detection and phenotypic-clustering in screens, and by the same token generate data rich “Precision Diagnostics” info of how cells respond (e.g. proliferate) in a variety of treatments.
Collaborative team and USPs:
- Platform for screening of CRISPR arrayed libraries to apply to high content cell-based screens.
- Extensive experience in development & use of live reporters (using CRISPR knock in) in human cell lines to simultaneously report on variety of phenotypes and processes (e.g. cell cycle)
- Pipeline in place for live timelapse imaging and single cell tracking through days
- Application of Deep Learning/Artificial Intelligence techniques for image analysis (cell segmentation & tracking) as well as for cell lineage analysis (learning, from feature-rich timelapse lineages, precise predictive signatures of proliferative potential and fate of cells/cell lines)
Outcomes:
- Identification of pharmacologically interesting gene leads
- Identification of novel dynamical phenotypic cell signatures
- Establishment of novel Precision Screening pipelines for Pharma (including use of experimental and AI/predictive analysis approaches)
- Establishment of cell-based Precision Diagnostics.
The studentship is sponsored jointly by AstraZeneca and the BCFN in Bristol with the majority of research to be conducted at Bristol. The 4-year funding will cover UK fees and will provide a stipend equivalent to the Research Council UK rate. The first year will be spent completing the taught component of the BCFN PhD programme, and years 2-4 will be spent working on the research project. For informal enquiries please contact Rafael Carazo Salas rafael.carazosalas@bristol.ac.uk.
Skills and qualifications:
- Skills desirable for this project include any of the following: cell culture, molecular biology including CRISPR & gene editing, live fluorescence microscopy, image analysis. Background in coding (MatLab) or statistical analysis (R) would be a bonus.
- The student should be highly motivated, have a 2:1 or first class degree in biological sciences, biochemistry or equivalent, and be experienced or eager to work with a highly interdisciplinary environment.
- The student must be eligible to work in the UK.
How to apply:
To apply go to http://www.bristol.ac.uk/study/postgraduate/2018/doctoral/phd-epsrc-bristol-centre-functional-nanomater/.
In the ‘Research Details’ section of the application form, please state that you are applying for the ‘AstraZeneca’ studentship.
Starting date: 17 September 2018