I completed my BSc (Hons) undergraduate degree at Newcastle University, graduating with a first class degree in Biomedical Genetics. During this time, I worked as a laboratory assistant at the Wellcome Centre for Mitochondrial Research in the Lightowlers lab, and was awarded a Biochemical Society summer vacation scholarship with Dr Monika Oláhová. During my PhD, I was an EMBO short term fellow in the laboratory of Dr Tom McWilliams.
Understanding the role of defective macroautophagy in congenital human disease
Principal Investigators: Professor Robert Taylor
Other Staff Members Involved: Dr Monika Oláhová
Our group uses whole exome sequencing (WES) to identify pathogenic mutations in novel mitochondrial disease genes. Mitochondrial disorders, however, are heterogenous in presentation so there is often clinical overlap with other inborn errors of metabolism. Using WES we have recently identified a cohort of patients with a congenital disorder of autophagy, an exceedingly rare group of disorders.
Autophagy is an intracellular process concerned with the recycling of nutrients, as well as the removal of toxic protein aggregates, damaged organelles (including mitochondria) and pathogens. Autophagy is therefore important during development and under stressful conditions such as starvation.
My project focusses on understanding how defects in autophagy contribute to the disease displayed by this cohort of patients. I use a range of imaging techniques including electron microscopy and cutting-edge high-resolution iSIM confocal microscopy, as well as molecular techniques, to investigate patient specimens including skeletal muscle and induced pluripotent stem cells (iPSCs).
Awards and presentations:
Awarded EMBO short-term fellowship (September-December 2019). This work was undertaken at Biomedicum, University of Helsinki, under the supervision of Dr Tom McWilliams.
Flash oral presentation at the EMBO workshop “Autophagy: From molecular principles to human diseases” (August 2019).
Poster presentation at 2020 European Society of Human Genetics 2.0 (June 2020).
Olahova M, Peter B, Szilagyi Z, Diaz-Maldonado H, Singh M, Sommerville EW, Blakely EL, Collier JJ, Hoberg E, Stranecky V, Hartmannova H, Bleyer AJ, McBride KL, Bowden SA, Korandova Z, Pecinova A, Ropers HH, Kahrizi K, Najmabadi H, Tarnopolsky MA, Brady LI, Weaver KN, Prada CE, Ounap K, Wojcik MH, Pajusalu S, Syeda SB, Pais L, Estrella EA, Bruels CC, Kunkel LM, Kang PB, Bonnen PE, Mracek Kmoch TS, Gorman GS, Falkenberg M, Gustafsson CM and Taylor RW (2021). POLRMT mutations impair mitochondrial transcription causing neurological disease. Nature Communications 12(1): 1135.
Thompson K*, Collier JJ*, Glasgow RIC, Robertson FM, Pyle A, Alston CL, Blakely EL, Olahova M, McFarland R, Taylor RW. Recent advances in understanding the molecular genetic basis of mitochondrial disease. J Inherit Metab Dis 2020;43:36-50. *Co-first authors
Oláhová M, Ceccatelli Berti C, Collier JJ, Alston CL, Jameson E, Jones SA, Edwards N, He L, Chinnery PF, Horvath R, Goffrini P, Taylor RW, Sayer JA. Molecular genetic investigations identify new clinical phenotypes associated with BCS1L-related mitochondrial disease. Human Molecular Genetics 2019;28:3766-76.
Sponsor/Funder: Wellcome Trust, Barbour Foundation, EMBO