Role of extracellular vesicles (EV) in neuron-astrocyte intercellular communication in neuronal death

Supervisor: Dr Mariaelena Repici

Co-Supervisor: Professor Andrew Devitt

Key words: extracellular vesicles, neuron-astrocyte communication, oxidative stress, cell death

 Applications are invited for a three-year Postgraduate studentship as part of the Aston Brain Health Cohort Study (ABaHCoS), co-funded by the Dunhill Medical Trust. The successful applicant will join the Aston Research Centre for Health in Ageing as part of an established research group working in molecular mechanisms of neurodegeneration under the supervision of Dr Mariaelena Repici. They will benefit from a tailored training programme including a range of research methodologies and dementia awareness training.

 The position is available to start in October 2024

Background to the Project

 Astrocytes are the most abundant glial cells in the mammalian brain. They have a neuroprotective effect on neurons by providing antioxidative function, releasing neurotrophic factors, reducing pro-inflammatory cytokines, and removing toxic aggregates. On the other hand, in stress conditions, stimuli released from damaged neurons can induce neurotoxic astrocytes that trigger neuronal death. Recently, the discovery of extracellular vesicles (EV) as important intercellular communicators has introduced a new perspective to this network. EV are released by neurons and glia and play a key role in synaptic activity, morphological plasticity, and neurovascular integrity. EV can also transfer disease-related molecules across the blood-brain barrier and can be detected in patients’ blood.

 The aim of the project is to define the functional significance of EV components in neuroprotection/neurodegeneration, to identify the role of EV-mediated neuron-astrocyte communication. We hypothesise that EV from healthy astrocytes protect neurons from oxidative stress and that this mechanism is perturbed in aging as well as neurodegeneration. The identification of the functional molecular cargo of astrocyte-derived extracellular vesicles in stress conditions will provide us with essential tools to identify early neuronal death and will help to define new strategies to prevent neurodegeneration.

 Objectives:

 1) generate differentiated neuron and astrocyte mono or co-cultures from human iPSC and validate their sensitivity to oxidative stress 

2) evaluate the effect of EV from healthy astrocytes on co-cultures of neurons and astrocytes in

in oxidative stress conditions, as well as the effect of EV from degenerating neurons on co-cultures of neurons and astrocytes in in control conditions

3) define the functional significance of the molecular cargo (proteomic, enzymatic activity, RNA sequencing) of such EV

4) Investigate changes in neuronal derived EV in the brain cohort to validate our in vitro results  

 The successful applicant will gain training in a multitude of techniques, ranging from iPSC differentiation into neurons and astrocytes, confocal imaging, analysis of extracellular vesicles, western blot, flow cytometry, liquid chromatography mass spectrometry (LC/MS) and proteomic analysis.

 Person Specification

 Candidates should have been awarded, or expect to achieve, EITHER: a] a First or Upper Second Class award in their Undergraduate Degree (Bachelors or UG Masters) from a UK institution, in a subject judged by Aston to be relevant to the proposed research. OR b] a Merit or above in a Postgraduate Masters degree in a relevant subject AND an Undergraduate Degree (Bachelors or UG Masters), both from UK institutions.  Degree subjects should be in Biology, Biomedical Sciences or Neurosciences. Preferred skill requirements include knowledge/experience of cell culture and microscopy. 

 Qualifications from overseas institutions will be also considered but performance must be equivalent to that described above, and the University reserves the right to ascertain this equivalence according to its own criteria.

 Contact information

 For formal enquiries about this project contact Dr Mariaelena Repici by email at [Email Address Removed]

 Submitting an application

 Your application must include:

1.   English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor degrees.

2.   A Research Proposal Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count.

3.   A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience. 

4.   Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary.

5.   Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage.

6.   A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Details of how to submit your application, and the necessary supporting documents can be found here. 

 Please select “Research Health Sciences” from the application form options.

 If you require further information about the application process please contact the Postgraduate Admissions team at [Email Address Removed]