I am a viral immunologist by training. My research has focused on cytoplasmic mechanisms that detect and inactivate viruses shortly after their entry to the cell. From 2009 to 2017 I worked in the lab of Dr Leo James at the MRC Laboratory of Molecular Biology in Cambridge, UK, where I co-discovered and characterised the novel antibody receptor TRIM21 as a potent antiviral sensor. In recent years I have been asking whether intracellular antibodies can be used to specifically degrade cellular proteins. This has led me into the field of protein misfolding. I am fascinated in the parallels between templated protein misfolding and viral infection and the shared mechanisms that may limit their spread.
Post-doctoral research associate
I have been interested in neurodegeneration from my MSc, and following on from myPhD, I knew that I wanted to focus my career on understanding the mechanisms of neurodegeneration. I carried out my PhD at the Babraham Institute, where I worked on the interaction between GIMAP6, a member of a family of small GTPases that play a role in maintaining lymphocyte populations, and GABARAPL2, an Atg8 homologue. This gave me an insight into autophagy and aspects of cell biology and equipped me for work in the Seaman group, which is based in the Cambridge Institute for Medical Research. Here I was given the opportunity to work on analysing the role endosome-to-Golgi trafficking plays in the trafficking and processing of the amyloid precursor protein and I have identified an important role for PLD3 in this process. Following on from this project, I was keen to broaden my knowledge of neurodegeneration further, and to this end, my project in the McEwan lab will focus on investigating the mechanisms via which TRIM21 can degrade antibody-bound aggregates in animal models of disease with the aim of uncovering the implications this has for various neurodegenerative disorders.
Post-doctoral Research Associate
I completed my PhD studies at the University of Heidelberg in Germany, working on a collaborative project between the groups of Dr. Thomas R. Jahn and Prof. Walter Nickel. My research focused on characterizing the unconventional secretion mechanism of the Alzheimer’s disease-associated tau protein and identifying the impact of this process on its trans-cellular propagation. Following my interest in neurodegeneration and protein aggregation, I joined the McEwan lab, where my work will be focusing on seeding templated propagation of disease-relevant tau species and the molecular mechanisms of generating fibrillar tau strains.
I completed an Undergraduate MSci in Molecular Cell Biology at the University of Glasgow. I spent one year at the bio-pharmaceutical company MedImmune in Cambridge where I used CRISPR/dCas9-VPR to activate genes of interest to increase biological drug expression. Following my degree, my interest in the molecular biology of misfolded proteins in Alzheimer’s disease lead me to the McEwan lab, where I am studying for my PhD. During my time here, I am investigating the mechanism of tau spread between cells. We aim to generate assays to distinguish between cytoplasmic and extracellular tau, a key problem in studying transcellular tau propagation.
As part of my BSc in Biological Sciences at Durham University, I undertook a placement year at MRC Technology (now LifeArc) at their Centre for Therapeutics Discovery. This provided an excellent experience in Drug Discovery where I worked on projects related to neurological disorders. Following my graduation from Durham in Summer 2017, I began working at the Alzheimer’s Research UK Drug Discovery Institute at Cambridge University. Generally, the aim of the institute was to identify therapeutics that modulate proteostasis, and typically protein degradation. This developed my experience in drug discovery and began my interest in protein degradation. I started my PhD in the McEwan lab in April 2019, where I am researching mechanisms of tau degradation by the ubiquitin proteasome system, funded by an Alzheimer’s Research UK studentship.
In 2018 I completed my MSci at UCL; I studied Biochemistry for the first two years, and then transferred to Cell Biology once I realised I was interested in more complex in vitro models of disease. My masters’ year project, in the Tedesco lab, focused on validating a lentiviral based stem cell therapy for Pompe disease using 2D and 3D human muscle constructs. I also became increasingly interested in neurodegeneration during this time, and the prion-like behaviour of proteins involved in diseases like Alzheimer’s and Frontotemporal Dementia (FTD). The opportunity to study the behaviour of these proteins in complex in vitro models is why I chose to join the McEwan lab. My PhD will focus on modelling the protein seeded aggregation of tau and other proteins involved in neurodegeneration, and look at the potential of antibody-TRIM21 mediated degradation to target misfolded proteins to the proteasome.
I completed my BSc in Biochemistry and Cell Biology at Jacobs University Bremen but did my final project in Immunology in the group of Prof. Dr. Sebastian Springer. My project was to uncover whether or not the dimerization of the murine cytomegalovirus immunoevasin gp40 is important for its function in immune evasion and so gain a better understanding of the interactions which take place between viruses and their hosts. I joined the McEwan lab because of my desire to apply immunological concepts in other seemingly unrelated fields. Throughout my time here I will be looking at TRIM21 mediated degradation of misfolded protein species implicated in neurodegeneration and exploring ways to exploit this pathway as a potential therapeutic. I will further developing TRIM21-based broadly-applicable methods of knocking down gene products at the protein level.
During my Biomedical Sciences BSc at the University of York I undertook a year in industry within the antibody discovery group at UCB Celltech. Whilst on this placement, I developed a particular interest in the molecular pathology of neurodegenerative diseases and how these pathways could be targeted by antibody-based therapies. This led me to the McEwan lab and my PhD project. I will be focusing on creating constructs using TRIM proteins to selectively degrade cytosolic proteins implicated in neurodegenerative diseases.
Undergraduate project student
I am currently completing a BSc in Medical Sciences specialising in neuroscience at the University of Exeter. Through this course, I have developed a deep interest in neurodegenerative disease. In order to explore this further and develop key laboratory skills, I am undertaking a placement year working on a collaborative project between the McEwan and Klenerman groups at the Cambridge DRI. The aim of my project is to compare the aggregation of different tau isoforms and visualise them using super resolution microscopy techniques.