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Lauren Overend

BSc Genetics, UCL


DPhil Candidate in Genomic Medicine and Statistics

Biography

I am a second year DPhil candidate on the Genomic Medicine and Statistics program, based at the Wellcome Centre for Human Genetics. As of September 2019, I am commencing my DPhil, working collaboratively in the Bashford-Rogers and Knight groups. I will be investigating the architecture of the B and T-cell Receptor repertoire during the disease course of sepsis.  

DPhil Project: 

Sepsis is as a life-threatening organ dysfunction caused by a dysregulated host response to often-unknown pathogens, with individuals exhibiting long-term immunosuppression following recovery. B and T-cells are vital components of the adaptive immune response and express a single surface B cell/T cell receptor (BCR/TCR) type respectively, for antigen binding. Diversity in receptors is generated by VDJ recombination and for BCRs, through somatic hypermutation and class-switching. The pool of BCRs and TCRs is termed the B/T cell repertoire. In healthy individuals this is highly diverse, yielding a complex immune architecture. However, studies suggest abnormalities in the repertoires of septic shock patients.  

I will generate the first comprehensive analysis of the BCR/TCR repertoire in sepsis using high-throughput BCR/TCR sequencing at multiple timepoints over the course of disease/recovery; one of the largest studies of this kind. Reactivation of Epstein Barr Virus (EBV) is common during sepsis and EBV induces B-cell somatic hypermutation. Therefore, I will use single-cell RNA sequencing to investigate the B-cell transcriptional profile associated with EBV reactivation in sepsis and relate to prognosis. Finally, I will investigate the effect of immunomodulatory therapies (steroids, anti-TNF) on the BCR/TCR repertoire, thus improving our understanding of how therapies can be combined in sepsis.

Background: 

Previously I was awarded a First Class Honors in BSc Genetics from University College London (UCL). As part of my undergraduate degree I undertook a final year research project on the ancient DNA analysis of historical leprosy. I also gained experience through several internships during my studies including: improving grain protein content in wheat (The John Innes Centre) and susceptibility of live stock to infectious disease (The Roslin Institute).