Alex Holmes

Alex Holmes

Profile

In October 2018, I started a BBSRC WR DTP funded PhD studentship in the Faculty of Biological Sciences and Faculty of Medicine and Health at the University of Leeds. I am currently working with Dr Antreas Kalli, Dr Jian Shi and Prof David Beech to determine the mechanism of activation and ion permeation of the Piezo1 mechanosensitive ion channel. Previously to this, I worked with Dr Antreas Kalli, Prof Adrian Goldman and Prof Colin Fishwick to study the structure and mechanism of membrane-integral pyrophosphatases. This is a highly multidisciplinary project involving novel computational biology and chemistry approaches in combination with laboratory-based biochemical and biomolecular techniques.

Prior to Starting this PhD Project, I did an integrated masters degree (MBiol) in Pharmacology at the University of Leeds. I graduated with a first class degree in July 2018. As part of this I did an extended research project under the supervision of Prof Adrian Goldman and Dr Vincent Postis. During this project, I validated Sf9 insect cells as a suitable expression system for two clinically relevant chlamydial transport proteins. During my undergraduate studies, I also worked with the TRPM2 ion channel in HEK-293 cells under the supervision of Dr Hugh Pearson and completed a research placement with Prof Arun Holden.

Research interests

Piezo1 is a mechanosensitive non-selective cation channel, which links mechanical force on the cell membrane to intracellular signal transduction. Piezo1 is found in the cells of hollow organs, the endothelial cells lining blood vessels and red blood cells. Both gain and loss of function mutation of this channel is associated with human disease. The activation mechanism for Piezo1 is not completely known.

Membrane-integral pyrophosphatases (mPPases) are clinically and agriculturally relevant proteins. They are responsible for the breakdown or production of pyrophosphate, coupled to the transport of a proton or sodium ion across a membrane. mPPases are an important area of study as they are not found in humans, but are found in human pathogens and are involved in critical cellular processes. Therefore, they represent novel drug targets against these species. Additionally, there is extensive research detailing the essential function of mPPases in plant species and for surviving abiotic stress conditions. This suggests that these proteins could be engineered to be more efficient, thereby improve plant yield in regions affected by global warming.

I am currently involved in several projects investigating the mechanism and structure of Piezo1 and mPPases through novel computational and laboratory approaches.

Qualifications

  • MBiol Pharmacology (1st Class), University of Leeds