Research Associate in Stem Cell Biology and Ageing

Ageing is the strongest risk factor for neurodegenerative diseases such as Alzheimer's disease (AD). Microglia, the brain's resident macrophages, are uniquely long-lived cells that regulate neurodevelopment, homeostasis, and repair. Unlike neurons or astrocytes, microglia exhibit innate immune memory, meaning that even subtle early-life challenges can prime them for exaggerated inflammatory responses later in life. In the ageing brain, this "primed" state evolves into a dysfunctional and senescent phenotype, characterized by impaired migration and phagocytosis, chronic inflammation, and secretion of neurotoxic mediators. Genome-wide association studies have identified microglial genes (e.g., CD33, TREM2, APOE) as key risk factors for late-onset AD, highlighting their central role in disease pathogenesis.

Recent studies in mouse models demonstrate that microglia are the dominant cellular drivers of age-related neurodegeneration. Chronic activation and sustained proliferation push them towards senescence, defined by replicative exhaustion, loss of regenerative capacity, and a senescence-associated secretory phenotype (SASP). Senescent microglia release inflammatory cytokines (IL-6, TNF, chemokines) that amplify neuronal injury and synaptic dysfunction. Thus, microglial senescence is emerging as both a hallmark and a driver of neurodegeneration.

Currently, it is critical to target microglia senescence for the treatment of neurodegenerative diseases. Our established senescence microglia cell model has been used for the drug screening and new drug discovery. Extracellular vesicles derived from induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-EVs) are a promising new approach. Our preliminary data demonstrate that iMSC-EVs strongly suppress microglial production of proinflammatory cytokines (IL-1β, TNFα, IL-6) in vitro, suggesting they may counteract senescence and restore microglial homeostatic functions. If validated, iMSC-EVs could represent a scalable, non-cellular therapeutic platform for age-related neurodegeneration.

This is an exciting opportunity for a fully-funded fixed-term (one year) research associate to work full time to advance our current human inflammatory-microglia in vitro ageing model for use in drug screening in the department of Life Science, at Manchester Met University. This project will involve working with scientists from the Ravan Bio research team.

The Role:

The role will involve culturing and differentiating human iPSCs into monocytes/macrophages, microglia and MSCs with our already established protocols and set in vitro inflammatory microglia ageing model with which relevant anti-ageing drugs and iMSCs-EVs will be validated. We are looking for someone with suitable knowledge and skill of iPSCs culture and differentiation into MSCs and microglia. Knowledge of immunology and its relation to inflammation and disease is desirable. This role will also involve presenting progress reports with our collaborators in the Rivan Bio.

Other duties and responsibilities include:

• Maintain accurate records of research conducted and carry out analysis of the results obtained using the most appropriate method.
• Work independently and in conjunction with other investigators and collaborators.
• Prepare research findings for publication and presentation.
• Participate in the activities of the research group via meetings and seminars
• Support dissemination of findings through delivery of workshops with potential stakeholders, including clinicians and industry

You will work within the Department of Life Sciences, which provide state of the art facilities located in the recently built, Dalton building. The Faculty of Science and Engineering is an exciting and dynamic environment in which to conduct cutting edge research.

Qualification we require:

• Hold a PhD in a relevant discipline
• Application Requirements: Experience in maintaining and differentiation of iPSCs

• Experience of the following would be advantageous:

• Experience of human iPSCs differentiation into mesenchymal stem/stromal cells (MSCs) and into monocyte/macrophages and microglia.

• Bioinformatics knowledge and RNA-seq data analysis.
• Molecular biology techniques such as RNA extraction, RT-q-PCR and Western blotting.
• Proficiency in statistical evaluation.

To Apply:

• To apply, please submit a CV and covering letter detailing your suitability, on the application portal.
• For an informal discussion, please contact; Dr. Baoqiang Guo ) and Prof. Chris Murgatroyd )

Develop your skills, further your knowledge and be part of a team who are transforming lives, every single day

Manchester Metropolitan University fosters an inclusive culture of belonging that promotes equity and celebrates diversity. We value a diverse workforce for the innovation and diversity of thought it brings and welcome applications from local and international communities, including those from Black, Asian, and Minority Ethnic backgrounds, disabled people, and LGBTQ+ individuals.

We support a range of flexible working arrangements, including hybrid and tailored schedules, which can be discussed with your line manager. If you require reasonable adjustments during the recruitment process or in your role, please let us know so we can provide appropriate support.

Our commitment to inclusivity includes mentoring programmes, accessibility resources, and professional development opportunities to empower and support underrepresented groups.

Manchester Met is a Disability Confident Leader and, under this scheme, aims to offer an interview to disabled people who apply for the role and meet the essential criteria as listed in the attached Job Description for that vacancy.

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