Postdoctoral Fellow: Neurodegenerative Disease Modelling Using Single Cell CRISPR screens (sanger)

Job Description

Do you want to help us improve human health and understand life on Earth? Make your mark by shaping the future to enable or deliver life-changing science to solve some of humanity’s greatest challenges.

We are seeking an outstanding postdoc to join an interdisciplinary team to help complete an exciting and ambitious project using cutting-edge techniques to study how genes associated with neurodegeneration contribute to disease in a cell-type-specific manner. This role is fixed term for 1 year with possibility of extension.

You will be part of a vibrant international Postdoctoral Fellow community at the Sanger Institute with a wide programme of transferable skills training and excellent career development opportunities.

About the role:

We are performing targeted CRISPR screens in multiple disease-relevant cell populations derived from human induced pluripotent stem cells (hiPSCs) and assessing the resulting phenotypes using a combination of single-cell RNA sequencing (scRNAseq) and high throughput cellular assays. The position will be based at Wellcome Sanger Institute under the leadership of Dr Andrew Bassett and Dr Sarah Cooper in collaboration with Dr Leopold Parts and Dr Florian Merkle. This project forms part of the Open Targets

(https://www.opentargets.org/) collaboration between academic and industrial partners to identify new drug targets for the treatment of neurodegenerative disease.

The successful applicant will work closely with another postdoc and a senior bioinformatician. The team has already identified top candidate genes associated with Alzheimer’s and Parkinson’s disease, built custom CRISPR libraries to knock out these genes, established differentiation protocols into neurons, astrocytes, and microglia and developed methods for single-cell CRISPR screening.

We are now at the exciting point of assessing the cellular phenotypes resulting from knockout using both scRNAseq and cellular assays. Applicants will have the opportunity to leverage these well-established CRISPR, differentiation and scRNAseq protocols and phenotyping assays, as well as developing or adapting new methods for phenotypic screening and more detailed follow-up studies in arrayed screens. Our aim is to identify and prioritise genes important for disease-relevant processes across multiple cell types, to reveal the underlying molecular mechanisms and new routes for therapeutic intervention.

Overall, this project represents an exciting opportunity to leverage recent advances in stem cells, CRISPR, and single-cell sequencing technologies, to drive innovation in disease-relevant cell models, develop assays to measure neurodegenerative phenotypes, and apply them at scale using the facilities at the Sanger Institute to advance our understanding of these disorders. It offers an outstanding career development opportunity for a highly-motivated applicant.

About you:

We encourage anyone with the Essential Skills to apply and especially welcome applications from individuals with expertise in the Desired Skills listed below:

Essential Skills

• PhD or equivalent experience in a relevant subject area e.g. Cell Biology, Molecular Biology, Neuroscience, or a closely related field.

• Exceptional interpersonal, and written and oral communication skills.

• Ability to work independently, collaboratively, and productively, as supported by a strong track record of first-author and collaborative papers in peer-reviewed journals

• Ability to develop, troubleshoot, and implement new assays and techniques

• Significant practical experience with core techniques in cell biology (e.g. mammalian cell culture and cellular assays) and molecular biology (e.g. genetics and sequencing)

• Excellent organisational and time management skills and a proven ability to work to tight deadlines.

Desired Skills

• Practical expertise with stem cell culture, directed differentiation, and forward programming

• Practical and theoretical expertise in neuroscience, neurodegeneration, disease modelling, and/or neuroinflammation

• In-depth knowledge of genome engineering techniques (including single cell or genome wide CRISPR screening)

• Experience with generation and analysis of genomics datasets (e.g. RNA-seq, ATAC-seq, ChIP-seq) especially single cell ‘omics, and experience with collaborating effectively with bioinformaticians.

• Practical expertise with advanced cloning techniques (e.g. recombineering, golden gate, Gibson assembly)

• Practical expertise with high-throughput cell-based functional assays (e.g. phagocytosis, cytokine release, autophagy, etc.) in either a pooled (e.g. FACS) or arrayed (e.g. Incucyte, high content microscopy, Luminex bead) setting.

Other information

The successful applicants would work as part of an interdisciplinary team with complementary strengths. The Cellular and Gene Editing Research group (https://www.sanger.ac.uk/science/groups/gene-editing-and-cellular-research-and-development) is interested in the development of genome editing techniques, cellular differentiation and cellular phenotyping systems, especially with respect to high-throughput investigation of gene and non-coding regulatory element function in neurodegenerative disease. The Merkle group (www.merklelab.org) has expertise in stem cell biology, neuroscience, cellular differentiation, CRISPR, and cellular phenotyping and has particular interest in combing these tools to modelling neurological diseases in vitro. The Parts group (https://www.sanger.ac.uk/people/directory/parts-leopold) is interested in applying statistical and bioinformatic tools to study biological problems, with a special interest in scRNAseq data and multi-‘omics integration, which will support and inform the wet biology aspects of the collaboration.

Open Targets is a pioneering public-private partnership between EMBL-EBI (European Bioinformatics Institute), the Wellcome Sanger Institute, GlaxoSmithKline (GSK), Celgene, Sanofi and Takeda, located on the Wellcome Genome Campus in Hinxton, near Cambridge, UK. Open Targets brings together expertise from six complementary institutions to generate evidence on the biological validity of therapeutic targets and provide an initial assessment of the likely effectiveness of pharmacological intervention on these targets, using genome-scale experiments and analysis. Open Targets aims to provide an R&D framework that applies to all aspects of human disease, to improve the success rate for discovering new medicines and share its data openly in the interests of accelerating drug discovery.

The Wellcome Sanger Institute and University of Cambridge offer a world-class academic environment, access to cutting-edge sequencing facilities, and extensive expertise in genome analysis and human genetics.

For further information and informal inquiries, please contact Andrew Bassett (ab42@sanger.ac.uk) and Sarah Cooper (sc34@sanger.ac.uk).

Joining us as Postdoctoral Fellow

When you join us as a Postdoctoral Fellow, you will benefit from a unique and well-resourced learning environment that will equip you for your future career. We are proud to produce and analyse genetic and cellular data on a scale unmatched by other institutes in Europe to advance biological and medical science.

You will be part of a vibrant international Postdoctoral Fellow community at the Sanger Institute with a wide programme of transferable skills training and excellent career development opportunities. We are committed to:

• Providing an enriching and respectful research environment so you can focus on and enjoy your work

• Mentoring you and providing opportunities for you to network across the genomics scientific community

For more information about being a Postdoctoral Fellow - please watch this short video: https://youtu.be/1-vxm2nBmFA

Additional information

Internal employees interested in applying for this role should apply through the internal Jobs Hub.

Applications: Please include a cover letter along with your CV. In your cover letter include detail on how your knowledge, skills and experience match the requirements of the role described.

Salary: £35,000 to £45,000 depending on experience, plus excellent benefits

Closing Date: 21-JAN-24

Contract duration: 1 year fixed-term (possibility of extension)

View our 2022-2023 Institute Highlights here: https://bit.ly/SangerHighlights

Hybrid Working at Wellcome Sanger:

We recognise that there are many benefits to Hybrid Working; including an improved work-life balance, with more focused time, as well as the ability to organise working time so that collaborative opportunities and team discussions are facilitated on campus. The hybrid working arrangement will vary for different roles and teams. The nature of your role and the type of work you do will determine if a hybrid working arrangement is possible.

Equality, Diversity and Inclusion:

We aim to attract, recruit, retain and develop talent from the widest possible talent pool, thereby gaining insight and access to different markets to generate a greater impact on the world. We have a supportive culture with the following staff networks, LGBTQ+, Parents and Carers, Disability and Race Equity to bring people together to share experiences, offer specific support and development opportunities and raise awareness. The networks are also a place for allies to provide support to others.

We want our people to be whoever they want to be because we believe people who bring their best selves to work, do their best work. That’s why we’re committed to creating a truly inclusive culture at Sanger Institute. We will consider all individuals without discrimination and are committed to creating an inclusive environment for all employees, where everyone can thrive.

Our Benefits:

We are proud to deliver an awarding campus-wide employee wellbeing strategy and programme. The importance of good health and adopting a healthier lifestyle and the commitment to reduce work-related stress is strongly acknowledged and recognised at Sanger Institute.

Sanger Institute became a signatory of the International Technician Commitment initiative In March 2018.  The Technician Commitment aims to empower and ensure visibility, recognition, career development and sustainability for technicians working in higher education and research, across all disciplines.