Postdoctoral Fellow | Neurodegenerative Disease Immune Response Modelling
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 perform an exciting and ambitious project using cutting-edge techniques with the aim to understand commonalities and differences in immune responses across neurodegenerative diseases (Alzheimer’s disease, Parkinson’s Disease and Amyotrophic Lateral Sclerosis).
The position will be based at Wellcome Sanger Institute under the leadership of Dr Andrew Bassett and Dr Sarah Cooper and will also benefit from a secondment position working under the leadership of Dr Sally Cowley at the University of Oxford where they will spend the first half of their contract.
The successful applicant will establish complex disease-relevant cellular models derived from human induced pluripotent stem cells (hiPSCs). These will be modulated using external stressors and genetic backgrounds, and the resulting phenotypes will be analysed using a combination of single-cell RNA sequencing (scRNAseq) and high-content imaging-based spatial assays that will allow comparison back to human patient samples to understand the disease-relevant phenotypes that can be modelled. This project is part of a broader programme of work also including patient sample analysis and cellular screening and forms part of the Open Targets collaboration between academic and industrial partners to identify new drug targets for the treatment of neurodegenerative disease.
The Wellcome Sanger Institute and the Cowley lab at the University of Oxford have an exceptional background in human disease genetics, iPSC-based cellular modelling, single-cell transcriptomic and single-cell spatial analysis, which will all be employed in this project. The successful applicant will work closely with a large team including other postdocs, staff scientists and bioinformaticians. This includes Dr Omer Bayraktar’s group who will be focusing on spatial and single-cell analysis of neurodegenerative disease patient samples.
The applicant will also interact closely with the computational teams of Magdalena Strauss, Mo Lotfollahi and Julio Saez-Rodriguez who will be focusing on single cell and spatial analysis, alignment of patient and cellular model data, understanding the effects of genetic perturbation and using AI/ML approaches to model these processes. This close interaction will allow a fully integrated, cross-comparison between cellular models and patient samples, giving a truly unique edge to this project.
Using the extensive expertise from the Cowley lab, the successful applicant will study cocultures of neurons, astrocytes and microglia in 2D and 3D with disease-relevant stressors to identify the best model system. Both single-cell transcriptomics, and custom cell paint panel/spatial transcriptomics will be used to phenotype the immune response within the cell models such as the microglial cell state, abundance of cells, cell-cell interactions. To understand the effects of genetics on the immune response we have access to iPS cell banks including known genetic neurodegenerative disease drivers, those with high/low polygenic risk scores and can use CRISPR techniques to generate new IPS models, all of which will be analysed using consistent single cell and high content imaging techniques.
Overall, this project represents an exciting opportunity to leverage recent advances in stem cells, single-cell sequencing and spatial transcriptomics as well as CRISPR, to drive innovation in disease-relevant cell models, develop assays to measure immune response in neurodegeneration, 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. We encourage anyone with the Essential Skills to apply and especially welcome applications from individuals with expertise in the Desired Skills listed below:
* PhD in relevant subject area (e.g. Cell Biology, Neuroscience, Molecular Biology or a closely related field), or on track to be awarded your PhD within 6 months of starting the role
* Proven ability to deliver research projects
* A track record demonstrating research excellence and expertise in your area of research
* 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. cloning and sequencing)
* Foster an inclusive culture where all can thrive and diversity is celebrated
* Motivation and ambition to make a personal contribution to Sanger Institute research
* Team player with the ability to work with others in a collegiate and collaborative environment
* Ability to effectively communicate ideas and results and present orally to groups
* Commitment to personal development and updating of knowledge and skills
* Ability to prioritise, multi-task and work independently
* Detailed orientated, strong organisational and problem-solving skills
Desired Skills
* Practical expertise with stem cell culture, directed differentiation, and forward programming
* Practical and theoretical expertise in neuroscience, neurodegeneration, disease modelling, and neuroinflammation
* In-depth knowledge of genome engineering and spatial techniques (including single cell or genome wide CRISPR screening, commercially available spatial platforms)
* 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 and single cell/spatial techniques (e.g. phagocytosis, cytokine release, autophagy, single cell techniques such as 10x, spatial work/high content imaging)
* Knowledge and understanding of public engagement in the context of the research environment, and ability to develop mutually beneficial initiatives and outcomes with public groups
Other information
The successful applicants would work as part of an interdisciplinary team with complementary strengths. The Cellular and Gene Editing Research group 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 Cowley group is interested in the role of microglia in neurodegenerative disease - we have developed methods for the differentiation of iPSC to microglia and have used these models to interrogate the role of neurodegenerative disease-associated genes (including a-synuclein, LRRK2, TREM2) in these innate immune cells.
Open Targets (OT) aims to systematically identify and prioritize drug targets by combining genetic, clinical, and functional genomics data. It is a collaborative initiative between the Wellcome Sanger Institute, a world-leading genomics institution; the European Bioinformatics Institute (EMBL-EBI), a global leader in the management, integration, and analysis of public domain life science data; and world-leading pharmaceutical companies.
The Wellcome Sanger Institute and the University of Oxford offer a world-class academic environment, access to cutting-edge sequencing facilities, and extensive expertise in genome analysis and human genetics.
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
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: £38,000 to £49,000 depending on experience, plus excellent benefits
Closing Date: 02-MAR-25
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.
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.
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