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BALR/APF Summer studentship: Martha Old



I was absolutely delighted to receive a BALR Summer Studentship and work under the supervision of Dr Alison John, Dr Iain Stewart and the team at the Margaret Turner Warwick Centre (MTWC) this summer, investigating idiopathic pulmonary fibrosis (IPF). My interest in IPF began during a genomics module in the second year of my BSc at the University of Bath. It was here that I became so interested in understanding the mechanisms of the disease. My project looked at “Understanding the functional role of RPAP1 in Idiopathic Pulmonary Fibrosis”. RPAP1 is a protein found in the RNA polymerase II complex, which is responsible for transcribing DNA to RNA.

IPF causes excessive lung scarring, with over 35% of the risk being attributed to genetic mutations in cells found in airspaces. These mutations lead to the dysregulation of proteins involved in the regulation of scarring and inflammation in the lungs. The Maragret Turner Warwick Centre at Imperial College London is dedicated to identifying mutations that might increase a person's susceptibility to developing the disease. This may then lead to the development of novel treatments for IPF that have higher efficacy than current therapies. My research built on from that of Dr Samuel Moss (University of Leicester) who, during his PhD at the MTWC, looked at a single nucleotide polymorphism (SNP) on the KNL1 gene that was associated with increased IPF susceptibility. His preliminary investigations indicated that this SNP was also associated with increased expression of RPAP1. This was significant as changes in RPAP1 expression have been connected to altered cell identity, a key factor in IPF pathogenesis.

In the first part of my project, I was able to develop my skills using R as a platform for data analysis, which I was completely new to. I used genome wide association study (GWAS) data and eQTL data to perform colocalization analysis which showed whether the same SNPs influenced both IPF susceptibility and RPAP1 gene expression. I also used single-cell RNA sequencing data to look at the patterns of RPAP1 expression in IPF and non-IPF control lung tissues, using immunohistochemistry to verify these findings. Additionally, I learnt tissue culture techniques and siRNA knockdown to assess the effects of removing RPAP1 from cells.  I then extracted RNA, converted it to cDNA, and used qPCR to confirm gene knockdown and analyse its impact.

This summer studentship was an incredible experience. I have learnt so many lab techniques, deepened my understanding of IPF got a real sense of what a research career will involve. The team at the MTWC was so supportive and I have especially grateful to Dr Iain Stewart and Dr Alison John for their mentorship. I am also grateful to Dr Maria Zarcone and Dr Samuel Moss for their help too. Whilst immensely challenging, the experience was so motivating and I have never been more sure that a career in science is what I want. The skills I have learnt will prove invaluable as I apply for PhD studentships and progress further in continue on my academic joureny. I am so very grateful for the opportunity to contribute to science this early on in my career. Thank you to the BALR and Action for Pulmonary Fibrosis, without whom this experience would not have been possible.

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