Postdoctoral Fellow

Job Title: Postdoctoral Fellow (Parkinson's Disease Experimental Research) Department: Physiology & Medical Physics Reporting to: Prof Jochen Prehn Location: RCSI, St. Stephen's Green, Dublin 2, Ireland Contract/Duration: Fulltime, contract for up to 23 months. Remuneration: IUA Post-doctoral Researcher Level 1 pt 2 Closing Date: 28th Feb 2025 RCSI is a community of academic, research, clinical and professional staff working collaboratively to lead the world to better health. Here, you will thrive in an innovative and inclusive atmosphere and your personal development and wellbeing will be supported. We invite you to join us to help deliver on our exciting mission "To educate, nurture and discover for the benefit of human health". We seek candidates whose experience to date has prepared them to contribute to our commitment to the "Race Equality Action Plan 2021-2024" at RCSI. Our students come from all walks of life and so do we. We hire great people from a wide variety of backgrounds. This makes our university stronger and ensures we hire the best talent. Innovating for a Healthier Future 2023-2027 is RCSI's new five-year strategic plan. Through it, RCSI will enhance human health by meeting the health workforce needs of society, creating the insights and inventions that drive health improvements, and working in partnership with patients and the public in support of better health and well-being for all. The strategy unites the RCSI community in supporting the UN Sustainable Development Goals - with a particular focus on Goal 3, which targets good health and well-being. For each of the last six years, RCSI has been positioned in the Top 300 of universities worldwide in the Times Higher World University Rankings. We are proud that RCSI ranks fifth in the world for "Good Health and Well-being" in the Times Higher Education #SDG #SDG Impact Rankings 2024. This reflects our commitment to supporting people of all ages to live healthy lives and our work to promote the concepts of well-being and positive health. Our values of Respect, Collaboration, Scholarship and Innovation continue to unite and direct our purpose. About Our Research RCSI recognises that excellence in research is critical to the quality of its educational activities, its credibility, and, overall, to its mission to enhance human health. RCSI's research strategy aims to build upon its strength in translational biomedical and clinical research to deliver transformational, high impact changes in health care. Targeting both Irish national and EU funding, along with increased collaboration with industry, is a major part of the RCSI research strategy. Forging increased collaboration between RCSI PIs and industry is of critical importance to achieving success in this area. RCSI is also committed to provide its researchers with the supports and developmental opportunities to enable them to continuously grow and support their overall career development. Summary of Post We are seeking a highly motivated and skilled post-doctoral researcher with strong experimental background in spatial/single-cell multi-omics, multiplex fluorescence imaging, associated bioinformatics techniques, and complementary systems modelling. The ideal candidate should be capable of independently designing and executing experimental research, while collaborating within a multidisciplinary team. Parkinson's Disease is the fastest growing neurodegenerative condition worldwide, yet the gold-standard treatment has remained largely unchanged for the last 50 years. The disease is characterised by the progressive degeneration of specific neuronal populations, such as dopaminergic neurons in the substantia nigra pars compacta . Another key pathological hallmark is the presence of intraneuronal protein aggregates, with a-synuclein as a central component. Despite significant research efforts, we still lack a complete understanding of molecular mechanisms driving cell type-selective vulnerability in Parkinson's. This post offers the opportunity to contribute to cutting-edge research aimed at transforming our understanding of Parkinson's. The JPND-funded 4DPD-Omics consortium is an international collaboration of experts in a-Synuclein biochemistry, neuroanatomy, neuropathology, disease modelling, spatial and single-cell omics, bioinformatics, and systems biology. This multidisciplinary initiative aims to perform a comprehensive spatiotemporal analysis of neuronal and non-neuronal responses to a-synuclein pathology in Parkinson's. The consortium has already generated extensive bulk transcriptomics and proteomics datasets from preclinical models and human post-mortem samples with a-Syn pathology. Through bioinformatics and functional investigations, key mechanisms such as mitochondrial dysfunction, metabolic rewiring, mitophagy/autophagy defects, proinflammatory processes, and synaptic vesicle trafficking alterations have been identified. However, critical questions remain regarding the specific cell types involved, temporal dynamics of these processes, and the signalling pathways driving these changes. The project will utilise well-characterized preclinical models and clinically annotated human post-mortem samples spanning Braak stages 0-VI. Advanced spatial transcriptomics, mass spectrometry, and CellDIVE multiplexing platforms will be employed to map whole transcriptome and proteome changes at spatial and single-cell resolution over time. These analyses will create a 4D dynamic atlas of cellular vulnerability and resilience, offering unparalleled insights into the molecular landscapes of Parkinson's progression. Key objectives include: Correlating cellular transcriptome/proteome changes with a-Syn pathology progression. Identifying biomarkers, pathways, and master regulators in susceptible and resistant cell subtypes. Validating findings in clinical samples using high-resolution multiplexing approaches, enabling single-cell profiling of 10,000 cells in tissue sections. Systematically investigating disease pathways in the context of cell-type-specific responses using systems biology and genome-scale modelling. The findings aim to identify novel biomarkers and therapeutic targets, paving the way for innovative drug development strategies. This position offers the opportunity to engage in cutting-edge research and collaborate with world-leading experts in the Parkinson's field. The successful candidate will contribute to the generation and integration of unprecedented datasets while advancing our understanding of cell type-selective vulnerability and disease mechanisms in Parkinson's. Specifically, the duties of the post are: Prepare and process tissue slices from pre-clinical models and human post mortem samples for spatial/single-cell transcriptomic/proteomic analyses and multiplex fluorescence imaging. Lead high-throughput spatial transcriptomics studies using the GeoMx Digital Spatial Profiler to investigate brain tissue samples from pre-clinical models, with a focus on a-synuclein pathology. Implement and optimise spatial single-cell transcriptomics/proteomics techniques to profile neuronal and glial subtypes across brain regions and time points. Perform multiplexed immunofluorescence imaging (MxIF) and CellDIVE hyperplexing to analyse tissue at single-cell resolution. Analyse spatial transcriptomics and proteomics data sets Collaborate closely with RCSI researchers and external partners to coordinate experimental design, data analysis, and integration across project work packages. Troubleshoot experimental challenges, refine methodologies, and maintain meticulous experimental records to ensure transparency and reproducibility. Communicate results through scientific publications, presentations at conferences and within the 4DPD-Omics network Collaborate with and support other researchers within the team as needed Ensure compliance with ethical guidelines for animal research and handling of human tissue samples. Comply with statutory legislation, RCSI, and department rules to maintain personal and workplace welfare and safety. Undergo training and professional development activities as required. Represent the best interests of the Department and RCSI at all times. Perform other duties as may be required from time to time. Qualifications - (Essential): PhD (or submitted PhD thesis) in Biochemistry, Molecular Biology, Cell Biology or related discipline, ideally in the field of neuroscience Demonstrated expertise in spatial transcriptomics, single-cell RNA sequencing, or similar advanced molecular techniques. Experience in translational research, particularly in neurodegenerative diseases, is highly desirable. Knowledge & Experience - (Essential): Demonstrated expertise in high-throughput spatial transcriptomics experiments, using platforms such as the GeoMx Digital Spatial Profiler and CosMx Spatial Molecular Imager, or similar technologies. Proficiency in high-resolution molecular imaging techniques, such as multiplexed immunofluorescence (MxIF) or CellDIVE hyperplexing. Experience with tissue processing (human and animal) for advanced molecular analysis. Experience with brain tissue is preferable. Ability to analyze complex experimental data, troubleshoot technical challenges, and propose innovative solutions. An understanding of the field of Parkinson's Disease or related neurodegenerative conditions A strong track record of impactful research, evidenced by high-quality publications. Excellent writing, interpersonal, and presentation skills Strong attention to detail, thoroughness and organisational skills, and ability to work to deadlines A collaborative mindset, with the ability to work both independently and as part of a team in a dynamic research environment Knowledge & Experience (Desirable): Experience in single-cell sequencing techniques, including library preparation, RNA probe collection, and analysis. Familiarity with spatial imaging systems such as the Leica CellDIVE and Vectra Polaris is an advantage. We are all too aware that imposter syndrome and the confidence gap can sometimes stop fantastic candidates putting themselves forward. We encourage you to apply - we would love to hear from you. Applications Please apply online through the RCSI careers portal before the closing date with your CV and cover letter detailing your applicable experience and motivation for applying for this role. Informal Enquiries can be directed to Prof Jochen Prehn () or Isabela Aparicio (). Please note we do not accept CVs directly.