This is a full-time, fixed term (3 year) position on Crick terms and conditions of employment.
The research group
We seek a talented, highly motivated and independent post-doctoral scientist to work on a project investigating the mechanistic basis of mitochondrial transfer between neurons and astrocytes in Mike Devine's laboratory at the Francis Crick Institute, with Nicola Corbett from MSD, and funded by an MSD-Crick Alliance award.
Dr Devine leads a group working at the interface between mitochondrial and neuronal biology. The group is broadly interested in how mitochondria can regulate neuronal (and in particular synaptic) function, and how such regulation is altered in neurological and psychiatric disease. Details of research projects currently being undertaken can be seen at: www.crick.ac.uk/research/labs/michael-devine. Research techniques used in the laboratory include transgenic mouse and human iPSC disease models, live cell imaging, genomic and transcriptomic analysis, electron microscopy.
Project summary
Mitochondria are critical organelles that power activity in almost all eukaryotic cells. Given the very high energy demands of the nervous system, mitochondrial dysfunction is implicated in the pathogenesis of a wide range of neurological disorders (Devine and Kittler, Nat Rev Neurosci 2018). Mitochondria are generally considered to be cell intrinsic; however, they are recognised to be capable of undergoing transfer between cells as functional and intact organelles (Spees et al. PNAS 2006). The aim of this project is to develop a more complete understanding of the process by which mitochondria can transfer between neurons and astrocytes specifically, with the future potential goal of harnessing this transfer for therapeutic purposes in diseases affecting the nervous system.
Understanding such neuron-astrocyte mitochondrial transfer has potential therapeutic implications, since upregulating this transfer in neurodegenerative disease might be a way of supporting and enhancing neuronal viability. However, much of the basic biology of mitochondrial transfer is unknown. The precise localisation and time course of transfer, and how it is regulated, are largely unknown. Furthermore, the exact mechanisms involved are unclear, although several pathways have been implicated (including macropinocytosis, phagocytosis, extracellular vesicles, and tunnelling nanotubes) which are potentially cell-type specific and context dependent.
This project aims to address this knowledge gap by furthering our understanding of the biology of mitochondrial transfer between neurons and astrocytes. To accomplish this goal, the project will study mitochondrial transfer in neuron/astrocyte co-culture systems. These will be used to study: (1) the location and time course of mitochondrial transfer, (2) how these dynamics change under conditions of mitochondrial or neuronal stress, and (3) how these are altered in a disease context. The initial focus will be on mouse primary hippocampal neurons and astrocytes from wildtype mice, and from mouse models of Parkinson’s disease (PD) for comparison, because PD is an archetypal neurodegenerative condition featuring neuronal mitochondrial pathology (Nguyen et al. Trends Neurosci 2019). If mouse experiments are successful, then human induced pluripotent stem cell (iPSC)-derived cortical neurons and astrocytes will also be used to understand transfer dynamics in human cells.
The longer term goal is to identify pathways that could be targeted to enhance mitochondrial transfer between neurons and astrocytes, as a potential modality for treating neurological diseases.
Postdoctoral Scientists are expected to lead their own projects, contribute to other projects on a collaborative basis (both in the lab and with external collaborators) and guide PhD students in their research. The ability to work in a team is essential.
Key experience and competencies
The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:
Essential
PhD in cell biology/neurobiology or in the final stages of PhD submission
Good working knowledge of mitochondrial biology and/or neurobiology
Experience in quantitative live cell imaging
Track record of writing papers as evidenced by publications or submitted manuscripts in referred journals
Effective written and verbal communication skills
Evidence of data presentation at scientific meetings
Experience of experimental design
Willingness to learn new experimental skills
Good organisational skills, ability to work independently and capable of interacting within a group
Desirable
Experience in primary neuronal and/or astrocytic culture
Experience in hiPSC culture and differentiation
Experience in image analysis
