This role has no closing date but will close subject to the right candidate being found
BRF Genetic Modification Service (GeMS) Senior Research Scientist
Reports to: Head of GeMS
This is a full time, fixed term (3 year) position on Crick terms and conditions of employment.
This project will involve a certain about of time in Oxford, but the role will be predominantly based at the Crick
The MRC National Mouse Genetics Network is a major new £22 million investment in mouse genetics for disease modelling that will capitalise on the UK’s international excellence in the biomedical sciences. The Network is comprised of challenge-led research clusters, with members distributed across the UK.
The Genetic Modification Service Group (GeMS), within the Biological Research Facility (BRF) at the Francis Crick Institute has received funding from the network to explore new technology for modelling large complex alleles in the mouse. Working initially in embryonic stem cells, we will explore site-specific nuclease and recombinase technologies for optimizing the large-scale engineering of the mouse genome. If successful, we will then adapt the protocols to achieve complex allele engineering in the mouse embryo.
Animal models provide an important means to determine gene function and model disease. The Biological Research Facility (BRF) are providing expertise and support for housing and experiment, all underpinned with world-class standards of welfare. Within the BRF, the Genetic Modification Services (GeMS) team provides the specialist skills and resources for the production, storage and use of genetically modified animals & cell lines.
Mutations associated with human disease can be engineered into the equivalent genes in mice, and the resulting genetically modified mice provide important insights into disease mechanism, revealing new targets for future medicines. Furthermore, these mouse models of human disease have considerable utility for preclinical testing of new medicines and can help the development of new tools to help disease diagnosis.
To date, most disease mutations that have been explored using mouse models are restricted to mutations which affect the DNA encoding proteins. Investigations into genetic variation in humans over the last decade, however, have revealed that mutations and variation in non-protein-coding DNA sequences and the overall structure of human genes play an important role in defining disease and disease-risk.
Significant differences also exist between mouse and human in these non-coding sequences and overall gene structure. Consequently, more sophisticated modelling of human disease mutations in the mouse is required. This is important both with respect to accurately modelling the human disease in mouse but also for testing new medicines that act on human gene products or new generation therapies that act upon on human primary gene sequences.
We need to develop tools that enable manipulation and assessment of DNA sequences at much larger scale than conventionally performed to allow an accurate investigation and modelling of human disease in mouse.
Methods have been reported by a few research teams around the world, but there is no clear best practice established for engineering the mouse genome in this way. UK researchers are able to access technologies for achieving simple modifications of the genome, through core facilities within their universities or via access to national and international programmes. There is, however, currently no capacity within the UK for the more sophisticated large-scale engineering in the mouse that our understanding of disease biology now demands.
Our project will address this unmet need. We will explore and optimize the different experimental parameters and compare different methodologies. We aim to establish robust pipelines for engineering complete human genes and synthetic segments into the mouse.
The technology and the resulting models will assist in our understanding of disease and the development of new therapies.
These include but are not limited to:
- Take responsibility for the planning, execution and analysis of high-quality research, ensuring the validity and reliability of data at all times
- Maintain ongoing scientific discussion with the PI and keep up-to-date knowledge of relevant publications
- Adapt existing scientific techniques and experimental protocols and develop new ones, when relevant
- Submit publications to high quality refereed journals
- Present work progress regularly and actively participate in group meetings and departmental seminars
- Represent and present the project at the MRC NMGN meetings as required.
- Contribute to the smooth running of the Group’s laboratories with other scientists, technicians and students
- Maintain highly organised and accurate records of experimental work and findings
- Act as a source of information and advice to other members of the group on scientific protocols and experimental techniques
- Carry out collaborative projects with colleagues in partner institutions, and research groups
Health & Safety
- Awareness and promotion of all relevant health and safety guidance and legislation.
- To ensure compliance to appropriate SOPs by all staff.
- To hold responsibility for reviewing and updating relevant SOPs, COSHH and RAs to share with staff as appropriate.
- Ordering consumables via a computer ordering system, always ensuring value for money and maintaining the budget for that service aspect.
- Use of appropriate storage and procedural databases.
- Using and training of others in all in house database systems appropriately.
- Reporting any issues with any in house database systems to the head(s) of service and cascading to appropriate working groups.
- Ability to interpret and communicate information effectively to staff across all levels.
- Building and maintaining effective relationships with project partners.
- Participating in committees and working groups.
- Providing written and verbal reports as required, including those related to scientific procedures and health and safety matters.
Key experience and competencies
The post holder should embody and demonstrate our core Crick values: bold, open and collegial, in addition to the following:
- A postdoctoral degree or equivalent in a biological subject or significant experience in a relevant area
- A proven track record in complex molecular biology and mammalian cell culture.
- Exhibit knowledge and understanding CRISPR/Cas design, gene targeting and associated techniques with some practical experience in the use of these techniques.
- Experience of using genome browsers and DNA analysis software.
- Interpretation, analysis and handling of sequencing data
- Commitment to continued professional development (CPD).
- Experience of contributing effectively to the work of a team with a flexible and collaborative approach.
- Ability to work independently and drive a project forward through good project planning, time-keeping, organisational and record-keeping skills.
- Good communication skills, both verbal and written with the ability to relay straight forward and complex information to a broad range of stakeholders.
- Good interpersonal skills enabling the post holder to influence and deliver at all levels
- Strong planning skills, the ability to prioritize in the face of competing demands, proven success in delivering work personally (and through others) to tight deadlines
- Good decision-making skills with the ability to use initiative and problem solve
- Mouse embryonic stem cell culture
- Experience of designing and implementation of genotyping strategies.
- Experience of supervising and training others to work to defined standard operational procedures