Postdoctoral Scientist | Neurobiology | Dr Michel Goedert | LMB 2253

Overall purpose: To work in the group of Dr Michel Goedert from the Neurobiology Division of the MRC Laboratory of Molecular Biology (LMB), as part of a programme aimed at understanding Molecular Mechanisms of Neurodegeneration. Specifically, to undertake research to develop methods for forming alpha‑synuclein filaments with the same structures as those from human brains. This work will be done in close collaboration with the group of Dr Sjors Scheres from the Structural Studies Division of the LMB.

The assembly of alpha‑synuclein into abnormal amyloid filaments is central to the development of several neurodegenerative diseases, including Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy. Since 2020, we have used electron cryo‑microscopy (cryo‑EM) to show that specific alpha‑synuclein determines the structures of alpha‑synuclein filaments from human brains. We have shown that specific filament folds define these diseases. Non‑proteinaceous densities of unknown composition are also present. To understand mechanisms of disease, one must be able to form filaments that have the same structures as those from human brains in vitro, in cells and in animals. This may require the addition of cofactors of known identity.

One successful candidate will use immunoprecipitation and mass spectrometry to identify the chemical identity of cofactors (in collaboration with Professor P. Barran, University of Manchester). The second candidate will develop methods for making alpha‑synuclein folds like those from human brains and use cryo‑EM to analyse these folds.

Key responsibilities:

• To undertake research aimed at understanding mechanisms of neurodegeneration.
• To identify, develop and apply a broad range of techniques to pursue the research objectives.
• To present scientific work at seminars within the laboratory and at external meetings.
• To contribute to laboratory‑wide discussions on developments within the field.
• To draft scientific papers and contribute to the overall preparation of research for publication.
• To contribute to the LMB’s mission in the public engagement of science and the translation of research findings into improvements in health care.
• To assist in the training of PhD students and other members of the LMB.

Within the overall direction of the programme, the group, the remit of the project and in discussion with the Group Leader, you will make a significant input into determining the direction of the project within a three‑year lifespan. To plan your own work and objectives on a 12‑month basis and manage your experimental work within the project along with your supervisor. To work with limited supervision to identify, develop, modify and apply the necessary techniques to achieve the goals of the project. To introduce and apply new techniques across a wide range of disciplines and to have the creativity and initiative to develop novel approaches and methods where required. To ensure the research is carried out in accordance with good practice and in compliance with local policies and legal requirements. To contribute to the smooth running of the group, including the effective use of resources, training of others and taking responsibility for use of communal facilities. To enhance your research and generic skills through a tailored development programme.

You will report to Dr Michel Goedert and you will interact and collaborate with other Postdoctoral Scientists, Research Support staff and Students, not only in your group, but also across the LMB and with external groups as necessary.

These positions are three‑year training and development positions for Postdoctoral Scientists who have recently completed their doctoral studies, are moving into a new research discipline or have limited experience of key transferable skills. We support Postdoctoral Scientists with a range of formal and on-the‑job training, including MRC training courses, external training and personal development courses, and one‑to‑one training with your Supervisor and other Scientists.

You will commit to undertaking the following:

• Developing and following a personal development plan.
• Attending training courses.
• Identifying additional training which will support you to develop your career.

Person specification: These should include a PhD in a relevant subject or to complete a PhD within 6 months.

Technical skills and expertise: The successful candidate will have experience in the generation of experimental models of amyloid formation and/or cryo‑EM/cryo‑ET. Experience in standard molecular biology techniques of cloning and cell culture or protein purification are essential. Experience in mass spectrometry can be an advantage. Track record of research: This will include contributions to published papers. Other relevant evidence of: Commitment, originality, ability to communicate, independent working, and working with others.

Applicants are required to submit a full CV and cover letter.