Project Title: Cell type-specific evolutionary and epigenetic signatures: leveraging human and non-human primate data to gain insight into brain disorder risk in humans
Supervisors:  Dr Nathan Skene, Professor Steve Gentleman, Dr Sarah Marzi
Location: Level 7, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ

About Me

During my undergraduate degree I was fortunate enough to spend a year at the University of Melbourne, where I took the Principles of Neuroscience module. With each lecture being vastly different but just as interesting as the last, I soon realised I would never be bored as a neuroscientist. As a result, I returned to King’s College London and specialised in neuroscience during my final year.

Before graduating I also had the opportunity to complete a year in industry, during which I investigated experimental therapies for sepsis and type 2 diabetes in small animal models at The William Harvey Research Institute in London. After graduating I worked as a research technician in the gut signalling and metabolism lab at LMS, where I investigated the role and regulation of a putative intestinal glucose sensor in murine pregnancy and lactation.

In 2019 I was awarded a 4.5 year MRC DTP Studentship. Having gained experience in the lab, I then wanted to understand how I could apply computational techniques to continue addressing scientific questions. As part of my studentship I completed the MRes in Experimental Neuroscience, during which I undertook three computational projects related to evolution, genomics, and neurodegenerative disease.

I am now a PhD student in the neurogenomics lab in the Department of Brain Sciences at Imperial College London. If my head isn’t buried in my laptop, then I’m either cooking or eating.

Qualifications 

• 2020-present: PhD Clinical Medical Research, Imperial College London (expected 2024)
• 2019-2020: MRes Experimental Neuroscience, Imperial College London
• 2014-2018: BSc Biomedical Science with extramural year, King’s College London 

Research Interests 

Studying evolutionary pressures on the genome can improve our understanding of human traits and disorders: sequence conservation is currently the best predictor of whether a genetic variant will be associated with human disease. Additionally, both autism and schizophrenia have been linked to genomic loci that have been under selective pressure. I am integrating transcriptomic, epigenomic, and primate genomic data to identify the cell types associated with the evolutionary pressures at key divergence points across primate evolution. Given that genetic risk loci predominantly fall into non-coding and regulatory regions, and changes in regulatory regions have been suggested to account for a greater proportion of adaptive evolution than changes in protein-coding regions, I will extend our modelling to measure selective pressures on regulatory regions. I will also evaluate how this relates to genetic risk for complex brain disorders such as Alzheimer’s disease.

Mentoring

Confront Educational Inequality mentoring program

Conferences

• Epigenetics in the Nervous System: Development and Disease, Berlin, 8-10 June 2022
  Poster and flash talk - CHAS, a deconvolution tool, infers cell type-specific signatures in bulk brain histone acetylation studies of brain disorders.
• Connectome, Brighton, 2-4 November 2022
  Talk - The effects of APOE on the epigenomic and transcriptional landscapes of human microglia in Alzheimer's disease
• Establishment and maintenance of brain cell states, Rungsted Kyst, 23-26 April 2023
  Poster and flash talk - Epigenetic regulation of microglia in a human-mouse chimera model of Alzheimer's disease
  Travel grant - Brain Prize, IBRO-PERC, and FENS travel grant
• ISMB/ECC3, Lyon, 23-27 July 2023
  Poster - Identification of genes, cell types, and phenotypes under selective pressure across primate evolution
  Travel grant - The genetics society junior scientist conference grant 

Selected publications

Manuscript in submission: Murphy, KB., Gordon-Smith, R., Chapman, J., Otani, M., Schilder, BM., Skene, NG. Identification of cell type-specific gene targets underlying thousands of rare diseases and subtraits (2023). medRxiv. doi: https://doi.org/10.1101/2023.02.13.23285820

Murphy, KB., Nott, A., Marzi, SJ. CHAS, a deconvolution tool, infers cell type-specific signatures in bulk brain histone acetylation studies of brain disorders. bioRxiv. doi: https://doi.org/10.1101/2021.09.06.459142

Collotta, D., Hull, W., Mastrocola, R., Chiazza, F., Cento, A. S., Murphy, C., Verta, R., Alves, G. F., Gaudioso, G., Fava, F., Yaqoob, M., Aragno, M., Tuohy, K., Thiemermann, C., & Collino, M. (2020). Baricitinib counteracts metaflammation, thus protecting against diet-induced metabolic abnormalities in mice. Molecular metabolism, 39, 101009. https://doi.org/10.1016/j.molmet.2020.101009

Al Zoubi, S., Chen, J., Murphy, C., Martin, L., Chiazza, F., Collotta, D., Yaqoob, M. M., Collino, M., & Thiemermann, C. (2018). Linagliptin Attenuates the Cardiac Dysfunction Associated With Experimental Sepsis in Mice With Pre-existing Type 2 Diabetes by Inhibiting NF-κB. Frontiers in immunology, 9, 2996. https://doi.org/10.3389/fimmu.2018.02996

Contact Details

Email:  c.murphy19@ic.ac.uk
LinkedIn: kitty-murphy-67804a216
Twitter: @kittybmurphy