Alex Whitworth

Alex Whitworth

Programme Leader

Genetic models of neurodegenerative disease

The survival of our most active tissues, such as the brain and heart, throughout decades of a human lifespan presents an extraordinary biological challenge. Mitochondria are central to the life and death of these tissues. While providing the high amount of energy required by these cells and buffering cytoplasmic calcium flux, they also produce many of the molecules that cause cellular damage and house a lethal arsenal of apoptotic cell death machinery. Thus, these organelles require extensive maintenance and quality control processes.

Failure in mitochondrial homeostasis is strongly linked to age-related conditions such as neurodegeneration. To perform the myriad essential cellular roles in complex cells such as neurons mitochondria must be extremely dynamic organelles. They are transported large distances to respond to localised demands for energy and calcium buffering, and undergo frequent fission and fusion events with each other and other organelles. The long-lived, post-mitotic nature of adult neurons permits the accumulation of oxidatively damaged macromolecules, and mitochondria are particularly susceptible. To combat this, damaged mitochondria are selectively degraded by autophagy, known as mitophagy. Two genes linked to Parkinson's disease, PINK1 and parkin, regulate mitophagy emphasizing the importance of this process to neuronal survival. However, much of our current understanding comes from in vitro studies, so we still have a poor understanding of this process in a physiological context.

Our group aims to understand the mechanisms of mitochondrial homeostasis in relation to neurodegenerative diseases such as Parkinson's disease and motor neuron disease. We use a combination of the powerful genetic techniques of Drosophila and molecular, cell biology and biochemical approaches in mammalian cells. Insights into these mechanisms will deliver a greater understanding of the role of mitochondrial maintenance in the health and dysfunction of the nervous system in a physiological context and will help guide therapeutic development to combat neurodegenerative diseases.

Research areas

Group Members

Research support

  • Wing Hei Au
  • Ana Terriente-Felix

Post-docs

  • Simonetta Andreazza
  • Victoria Hewitt
  • Leonor Miller-Fleming
  • Alvaro Sanchez-Martinez
  • Roberta Tufi

Post-graduate students

  • Thomas Gleeson
  • Juliette Lee

Publications

Biography

Career history

2015-Present
Programme Leader, MBU
2014-2015
Reader in Neurogenetics, University of Sheffield
2011-2013
Senior Lecturer, Biomedical Sciences, University of Sheffield
2005-2010
Lecturer, Biomedical Sciences, University of Sheffield
2001-2005
Post-doctoral research fellow, Genome Sciences, University of Washington. advisor: Dr Leo Pallanck
1997-2001
PhD, Genetics, University of Cambridge. advisor: Dr Steven Russell
1993-1997
BSc, Biochemistry, Imperial College London

Activities and distinctions

Editorial Board Member - PLoS ONE and Scientific Reports
Reviewer for: Science, Nature Neuroscience, Molecular Cell, Proc Natl Acad Sci USA, Current Biology and others
Invited Speaker: Keystone Symposium - Parkinson’s Disease: Genetics, Mechanisms and Therapeutics
Invited speaker: Euromit 2014