Determining the role of epigenetic regulation in neurodegenerative diseases
The likelihood of someone developing dementia is influenced by a combination of their genetics and the environment they are exposed to. However, it is not clear how these factors interact with each other to affect cells in the brain. One possible mechanism is through epigenetics – chemical modifications to the genetic material in cells that regulate gene expression.
The Marzi Lab aims to determine the role of epigenetic regulation in neurodegenerative diseases, including Parkinson’s, Alzheimer’s disease and motor neuron disease, using state of the art epigenetic and genomic techniques in cell populations and at the single cell level. The team's research has the potential to identify an epigenetic link between genetic and environmental risk in dementia and identify mechanisms by which these risk factors make cells susceptible to neurodegeneration. The aim of this research is to reveal opportunities and avenues for new therapies for neurodegeneration and dementia.
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Dr Sarah Marzi
Dr Sarah Marzi is a Group Leader at the UK DRI at King's. Find out more about her career and expertise on her profile page.
Research summary
The study of how these factors affect epigenetic processes - a collection of biochemical mechanisms that regulate the levels, location and timing of gene expression - is emerging area of interest in dementia and neurodegeneration. Credit: Shutterstock/Juan Gaertner
Epigenetic regulation of environmental and genetic risk in neurodegenerative disease
While it is known that genetic variants and environmental factors contribute to the risk of developing neurodegenerative diseases, the biological mechanisms involved remain largely unknown. An emerging area of interest is the study of how these factors affect epigenetic processes, a collection of biochemical mechanisms that regulate the levels, location and timing of gene expression.
Dr Sarah Marzi is an expert in epigenetic regulation, particularly in relation to human disease. She has expertise in advanced sequencing techniques, including those sensitive to epigenetic modifications, working with human brain tissue as well as in vivo and in vitro model systems. The Marzi Lab combines these experimental techniques with innovative statistical and computational analytical methods in their research.
In her UK DRI programme, Dr Marzi is studying functional epigenetic pathways and mechanisms in Parkinson’s and Alzheimer’s diseases. One of Dr Marzi’s core interests lies in the immune cells of the brain. There is growing evidence that disease-associated microglia states play an important role in how genetic variants influence Alzheimer’s disease. The Marzi Lab aims to identify the upstream regulatory mechanisms that control microglia state transitions and observed gene-environment interactions.
Evidence also suggests that certain environmental factors, particularly several types of agricultural pesticide, can increase the risk of Parkinson’s disease. As the mechanisms via which these environmental risk factors act on disease are not clear, the Marzi Lab is investigating how epigenetic processes may be playing a role.
Main objectives and research goals:
- Determine how gene regulation is altered in specific disease-relevant cell types in an environmentally-induced Parkinson’s disease model.
- Identify where the earliest molecular changes occur.
- Determine cell-type specific vulnerabilities to exposure to the pesticide rotenone.
- Identify how non-coding genetic risk variants relate to environment-driven regulatory changes.
Key publications
Vacancies
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Key details
- Location UK DRI at King's
- Salary: £45,031 - £52,514 per annum
About the role:
Dr Sarah Marzi https://ukdri.ac.uk/team/sarah-marzi) is seeking to appoint a Research Associate. Her research programme aims to determine the role of epigenetic regulation in neurodegenerative diseases, Parkinson’s and Alzheimer’s disease, using state of the art epigenetic and genomic techniques in cell populations and at the single cell level. We are seeking a postdoctoral researcher to work on epigenetic and transcriptional profiling of toxicant exposures and Parkinson’s in cell and animal models as well as postmortem human brain tissue.
The successful candidate should have laboratory experience in epigenetics techniques, particularly chromatin profiling. Prior experience in single cell genomics approaches is essential. You will be a dynamic, creative, and motivated scientist interested in pursuing questions deeply. With strong molecular biology experience of genomic/epigenomic approaches, you will use a range of methods for cell and brain tissue analyses including next generation RNA sequencing, ChIP sequencing and CUT&Tag (or equivalent) and ATAC sequencing methods, and particularly 10X single cell multiome profiling.
The Marzi Lab is highly collaborative. You will join a multidisciplinary team on the Denmark Hill Campus with a leading role in:
- Designing and performing experiments
- Developing technical advances
- Performing data analysis
- Presenting the results
- Writing up manuscripts to be submitted to peer-review journals
About you:
To be successful in this role, we are looking for candidates to have the following skills and experience:
Essential criteria
- Hold a PhD in Molecular Biology, Neuroscience or a closely related discipline, or equivalent research, industrial or commercial experience
- Practical experience within a research environment and publication in relevant and refereed journals and ability to conduct a detailed review of recent literature
- Knowledge of gene regulation and chromatin biology, particularly in the context of neurodegenerative diseases.
- Practical experience in a broad range of standard laboratory techniques including light microscopy and molecular biology (e.g., immunofluorescence on brain tissue, cloning, qPCR, cell culture
- Practical experience single cell or single nuclear genomics methods, including experience with dissociation protocols from low input material
- Excellent written communication skills and the ability to write clearly and succinctly for publication
- Willingness to work as part of a team and to be open-minded and cooperative
- Practical experience with epigenetic assays, including any of the following:
- ChIP-seq
- ATAC-seq
- CUT&Tag
Desirable criteria
- Experience working with bio-banked tissue
- Familiarity with neuroanatomy and/or immunology
- Knowledge of Parkinson’s disease genetics and neurobiology
Lab members
Collaborators
Lab funders
Thank you to all those who support the Marzi Lab!