Postdoctoral Research Scientist

This post will investigate how Parkinson's disease-associated genetic perturbations alter mitochondrial function and cellular metabolism in human neurons. The postholder will extend, quality-control and use focused CRISPRi/a sgRNA libraries in iPSC-derived cortical neurons and validate priority findings in iPSC-derived dopaminergic neurons. Cellular responses will be characterised using established high-content imaging, quantitative cellular phenotyping and assays of neuronal metabolism, under the supervision of Dr Brent Ryan in the Department of Physiology, Anatomy and Genetics. The successful candidate will be based in the Ryan Group within the Laboratory of Molecular Neurodegeneration at the Kavli Institute for Nanoscience Discovery, South Parks Road, Oxford. The group has established expertise, protocols and experimental platforms for CRISPRi/a functional genomics, sgRNA design and cloning, iPSC culture and neuronal differentiation, high-content imaging, mitochondrial phenotyping and quantitative data analysis. We welcome candidates with strong practical experience in one or more relevant areas, including CRISPR or molecular biology, functional genomics, iPSC or neuronal culture, high-content imaging, mitochondrial biology, cellular metabolism or quantitative cell biology. Training, established protocols and support from experienced members of the group will be provided for methods outside the successful candidate's existing expertise. Working within a collaborative and interdisciplinary research environment, the postholder will integrate these approaches to identify how common and rare Parkinson's-associated genes affect neuronal mitochondrial biology, define shared cellular mechanisms and prioritise findings for further validation. The role provides an opportunity to build on the candidate's existing strengths while developing broader expertise across functional genomics, human neuronal models and quantitative cellular phenotyping.,

• Maintain iPSC cultures and differentiate iPSC lines into dopaminergic or cortical neurons.
• Perform medium-throughput experiments in iPSC-derived neuronal models using small-molecule treatments and CRISPR-based genetic perturbations.
• Create and maintain sgRNA libraries to enable CRISPR-mediated manipulation of disease-related genes in neurons
• Apply, develop and optimise cellular, molecular, high-content imaging and metabolic assays to assess mitochondrial, organelle and broader neuronal phenotypes relevant to neurological disease.
• Select, adapt and develop experimental protocols and determine the most appropriate methodologies to test hypotheses, identifying alternative approaches when technical problems arise.
• Use specialist scientific equipment in a laboratory environment.
• Gather, analyse, interpret and present scientific data from a variety of sources, refining working hypotheses as appropriate.
• Manage own research and administrative activities, including small-scale project management and coordination of multiple strands of work to meet deadlines.
• Contribute ideas for new research projects and to wider project planning.
• Contribute to the development of research proposals and ideas for generating research income.
• Collaborate in the preparation of scientific reports, journal articles and other research outputs, and present data, papers and posters at conferences, seminars and external meetings.
• Act as a source of information and advice to other members of the group on scientific protocols, experimental techniques and relevant methodologies.
• Collaborate effectively with other members of the research group and with colleagues in partner institutions and research groups to achieve shared project goals
  
  Hold a PhD/DPhil in neuroscience or cell/molecular biology or equivalent
• Have experience in neuronal/glial cell culture, preferably in human pluripotent stem cells
• Have experience in setting up cellular assays, such as image-based experiments
• Have knowledge of neurodegenerative disorders
• Be highly motivated, with the capacity to think creatively and work across teams
• Experience of creating collaborative and inclusive environments with people from different backgrounds., Understanding of lysosomal and mitochondrial biology, and related cellular pathways
• Experience with implementing CRISPR methodologies
• Experience with implementing methodologies such as Cell Painting and metabolic flux assays
• A strong track record of contribution to scientific publications
• Experience with analysis pipelines of microscopy images
  
  Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford, OX1 3QU, At the Department of Physiology Anatomy & Genetics (DPAG) we undertake discovery science where we reassemble physiological processes at the molecular, cellular, tissue and systems level of organisation. In so doing we provide a bridge to translational medicine, and interface between physical and life sciences. We are committed not only to innovative research and the highest standard of teaching, but also to creating an inclusive and supportive working environment.
  
  Your wellbeing at work matters, so we offer a range of family friendly and financial benefits including:
• An excellent contributory pension scheme
• 38 days annual leave
• A comprehensive range of childcare services
• Family leave schemes
• Cycle and electric car loan schemes
• Employee Assistance Programme
• Membership to a variety of social and sports clubs
• Discounted bus travel and Season Ticket travel loans
While this is a full-time role, we welcome applications from individuals who wish to be considered for flexible working arrangements.