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 determine 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. Main duties: • 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. Key responsibilities: 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. Working relationships: 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. Additional information: 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. • 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 Academic qualifications: These should include a PhD in a relevant subject or due 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. • Working with others. Additional information: Applicants are required to submit a full CV and cover letter. Corporate/local responsibilities & requirements You must carry out your responsibilities with due regard to the UKRI: • Code of Conduct • Equality, Diversity and Inclusion policy • Health and Safety policy • Data Protection policy Job descriptions should be reviewed on a regular basis and at the annual appraisal. Any changes should be made and agreed between you and your manager. The above lists are not exhaustive and you are required to undertake such duties as may reasonably be requested within the scope of the post. All employees are required to act professionally, co-operatively and flexibly in line with the requirements of the post, the MRC and UKRI. The role holder will be required to have the appropriate level of security screening/vetting required for the role. UKRI reserves the right to run or re-run security clearance as required in the course of employment. UKRI - UK Research and Innovation UKRI is an organisation that brings together the seven disciplinary research councils, Research England and Innovate UK. Together, we build an independent organisation with a strong voice and vision ensuring the UK maintains its world-leading position in research and innovation. Supporting some of the world's most exciting and challenging research projects, we develop and operate some of the most remarkable scientific facilities in the world. We are pushing the frontiers of human knowledge through fundamental research and delivering benefits for UK society and the economy through world-class research, skills and business-led innovation. More information can be found at www.ukri.org. Choosing to come to work at UKRI means that you will have access to a whole host of benefits from a defined benefit pension scheme, excellent holiday entitlement, access to employee shopping/travel discounts and salary sacrifice cycle to work scheme. For more details, visit benefits of working for UKRI. How we support EDI in the workforce At UKRI, we believe that everyone has a right to be treated with dignity and respect, and to be provided with equal opportunities to thrive and succeed in an environment that enables them to do so. We also value diversity of thought and experience within inclusive groups, organisations and the wider community. For further information, please visit 'How we support EDI in the workforce'. Disability Confident Employer As users of the disability confident scheme, any candidate who opts into the scheme and best meets the essential criteria, will be shortlisted for interview. We will ensure that individuals with disabilities are provided reasonable accommodation to participate in the job application or interview process, to perform essential job functions, and to receive other benefits and privileges of employment. Please contact us to request accommodation. How to apply Online applications only preferred for this role. Please submit a CV and covering letter which clearly outlines how you fulfil the criteria specified along with your motivation for UKRI and the role. Ensure that the job reference number is included in the filename description of each document uploaded. Note that failure to address the above criteria or submit an application without a covering letter may result in the application not being considered. Assessment will only be based upon the content of your submitted covering letter and CV and not the 'experience' section of the application. UKRI seeks to ensure it creates and maintains a system of openness, fairness and inclusion - a collaborative, trusted environment, which is attractive to and accessible to everyone who is interested in developing their career with us. Artificial intelligence can be a useful tool to support your application, however, all examples and statements provided must be truthful, factually accurate and taken directly from your own experience. Where plagiarism has been identified (presenting the ideas and experiences of others, or generated by artificial intelligence, as your own) applications may be rejected and internal candidates may be subject to disciplinary action. As part of the pre-employment checks there is a requirement to undergo Baseline Personnel Security Screening. BPSS is a pre-condition of employment and failure to achieve it may mean that the employment offer is rescinded. UKRI reserves the right to run, or re-run, security clearance as required during the course of employment. The MRC Laboratory of Molecular Biology (LMB) is one of the birthplaces of modern molecular biology and has played an important role in the development of many new techniques, most notably X-ray crystallography of proteins, DNA sequencing and monoclonal antibodies. The LMB has a clear goal of understanding biological processes at the molecular level, with the ultimate aim of using this knowledge to tackle specific problems in human health and disease. We aim to tackle difficult, long-term problems, which often require investment over many years. There are four scientific Divisions - Structural Studies, Protein and Nucleic Acid Chemistry, Cell Biology and Neurobiology. However, scientific collaboration between the different Divisions is extensive. Scientists are well supported by excellent scientific facilities and by the LMB Operations Group which maintains the core infrastructure and services of the institute. Our state-of-the-art laboratory provides an unsurpassed environment for both young and established researchers. Scientists are drawn to the LMB from all over the world, thus creating a lively and international community for the exchange of ideas and technical innovation. The LMB is a great place to work and progress your career, be it in scientific research or the support functions. The LMB is a unique working environment where our researchers are rewarded by world class innovation and collaboration opportunities that the LMB name brings. The LMB is an excellent place to develop yourself further and a range of training & development opportunities will be available to you, including professional registration with the Science Council. Choosing to come to work at the LMB (part of UKRI) means that you will have access to a whole host of benefits from a defined benefit pension scheme and excellent holiday entitlement to access to employee shopping/travel discounts and salary sacrifice cycle to work scheme, as well as the chance to put the LMB and UKRI on your CV in the future. We actively support equality, diversity and inclusion in all our activities, processes and culture. We encourage applications from all sections of society irrespective of gender, race, ethnic or national origin, religion or belief, sexual orientation, disability or age. We are a disability inclusive employer and encourage disabled people to apply for this role. You are very welcome to contact us for information about the application process and any adjustments you may require; recruit@mrclmb.ac.uk. 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