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.
Are you interested in high-throughput single-cell CRISPR screening in human cell models and AI to uncover therapeutic vulnerabilities in neurodegenerative disease?
Here at the world-famous Wellcome Sanger Institute, we are seeking an enthusiastic, motivated Staff Scientist to join an interdisciplinary team to help to study how genes associated with neurodegeneration contribute to disease in a cell-type-specific manner using CRISPR-screening and deep learning.
This is a 3-year fixed-term contract.
About the role
The position will be based between the wet lab group of Dr Andrew Bassett and Dr Sarah Cooper and work closely with Dr Mo Lotfollahi to contribute to a collaborative project with the Lotfollahi Lab. This project forms part of the Open Targets collaboration between academic and industrial partners to identify new drug targets for treating neurodegenerative disease.
As a Staff Scientist, you will perform targeted combinatorial CRISPR-screens with a set of identified top candidate genes associated with neurodegenerative disease such as Alzheimer's and Parkinson's disease and build custom CRISPR libraries to knock out these genes and their combinations. You will use established differentiation protocols to generate neurons, astrocytes, and microglia and their cocultures and perform single-cell 'omics and cellular phenotypic assays such as endo-lysosomal function, ER stress or cell painting on the resulting cells.
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. These datasets will be fed to generative AI methods to predict unmeasured perturbations, and an important aspect of this project will be the validation of these predicted perturbations in the lab. As part of this position, we will support you to develop your computational skills and learn concepts about machine learning.
About you
To excel in this role, you will need the following (essential):
- PhD or equivalent experience in a relevant subject area e.g. Genetics, Cell Biology, Molecular Biology.
- Ability to work independently, collaboratively, and productively, as supported by a strong track record of first-author and collaborative papers in peer-reviewed journals.
- Proven experience of mammalian cell culture.
- Ability to test and implement new assays and techniques including their troubleshooting.
- In depth knowledge of genome engineering techniques, stem cell biology (especially in vitro differentiation) and/or neurodegenerative disease.
- Experience in molecular biology techniques e.g. vector design and construction, high throughput sequencing library prep, etc.
- Self-motivated with an ability to work independently on projects as well as part of a team and lead experimental design and execution up to the point of publication.
- Exceptional written and oral communication, organisational and presentation skills.
- Ability to work to tight deadlines.
Desirable:
- Detailed knowledge of neuronal, astrocyte, or microglial biology and their roles in neurodegeneration.
- Practical experience with human iPS or ES cells.
- Experience of single cell 'omics assays.
- Experience with in vitro differentiation of mouse or human stem cells.
- Practical experience with genome engineering techniques (e.g. CRISPR).
- Practical expertise with advanced cloning techniques (e.g. recombineering, golden gate, Gibson assembly).
- Experience in phenotypic assay development in either a pooled (e.g. FACS) or arrayed (e.g. Incucyte, Luminex bead) setting.
- Experience with generation and analysis of genomics datasets (e.g. RNA-seq, ATAC-seq, ChIP-seq) especially single cell 'omics.
- Experience in computational analysis of single-cell data using R or Python packages (e.g. scanpy or Seurat).
About us
As a Staff Scientist you will 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 Lotfollahi lab develops state-of-the-art generative machine learning tools that can model cellular behaviours across various modalities and scales. You will work within an interdisciplinary team of wet and computer scientists, with a shared goal of improving our understanding of the rules of life and using this to improve health for all.
Open Targets 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 such as GSK, Sanofi, MSD, Pfizer, and Genentech.
Additional information:
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:£44,800 - £53,800
Closing Date:Sunday 16-FEB-25
Contract duration:3 years fixed term.
View our 2023-2024 Institute Highlights here: bit.ly/SangerHighlights2023-24
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.
