Professor Zofia Chrzanowska-Lightowlers
Professor of Mitochondrial Biology
As a Professor of Mitochondrial Biology I have a keen interest in the post-transcriptional gene expression in the human organelle. My motivation as a scientist is to uncover and understand the basic molecular mechanisms that govern mitochondrial RNA metabolism and in these endeavours I collaborate closely with Prof Bob Lightowlers.
Our work on protein synthesis in human mitochondria has been enhanced by interactions with our collaborators across mitochondrial groups in Europe. Our collaborations also extend into non-mitochondrial groups to improve our understanding of protein synthesis including past, present and projected interactions with Prof Warren Tate (New Zealand), Prof Tatsu Abo (Japan), Prof John Atkins (USA) and Prof Andrew Crosby (Exeter).
The mitochondrion is an organelle found in all nucleated cells of higher eukaryotes. It is the site of oxidative phosphorylation and contains its own genome that encodes 13 proteins, which are essential components of the respiratory complexes and the ATP synthase. In addition to the mRNAs the genome also encodes the 22tRNAs and 2 rRNAs that are required for this intra-mitochondrial protein synthesis.
It is the fate of these mitochondrial mRNA species that we are investigating. Although much is known about the turnover of cytosolic and bacterial transcripts, until very recently almost nothing was clear about the mitochondrial RNA species. Do they behave as their bacterial ancestors or follow the example of the cytosol in which they reside ? What is the normal decay mechanism and what are the enzymes responsible for carrying out these activities ? We have identified that in contrast to yeast, the mammalian mt-transcripts are polyadenylated but the function of this tail is not yet certain. In bacteria it enhances decay, whilst in the eukaryote cytosol it is bound by poly(A) binding proteins and promotes both stability and translation.
Since the mitochondrial genome cannot yet be manipulated we have used cell lines with identified mutations to try and answer some of these questions. Most of the mt-mRNAs require polyadenylation to generate the Stop codon. By using a cell line that has a 2 base pair microdeletion the resulting mRNA loses the termination codon we have identified a ‘non-stop’ decay mechanism and shown that in this situation the poly(A) tail confers stability to the aberrant transcript.
Our work is presently focussed on identifying the mitochondrial nucleases and mt-RNA-binding proteins involved in the mechanism described above as well as those involved in the normal decay pathway and characterising their specificity. We are also looking at the ways in which the organelle can exert a level of ‘Quality Control’ and the protein factors that are likely to be responsible for this activity.
Within our department the link between pure and clinical research is very strong and described above. Many of the neurological conditions that patients present with affect their mitochondrial DNA. In some instances this would be predicted to affect the subsequent transcription and translation. This provides the opportunity to study the differences in the homeostasis of mitochondrial mRNA in controls versus disease.
- Biochemical Society’s Theme Panel I – Genes
- Biochemical Society’s ‘Local Ambassador’
- Member of Pathological Society since 2008
- Member of Biochemical Society since 2000
- Wellcome Trust Research Career Development Fellowship, February 1999 – 2003
- The Don Beaven Travelling Fellowship
- Christchurch School of Medicine, University of Otago, New Zealand, February 1998
- Sir Henry Wellcome Commemorative Award for Innovative Research, June 1997
- Ph.D. Regulation of the Homeostasis of Cytochrome c Oxidase, University of Newcastle upon Tyne, England, May 1995
- M.Sc. Biochemistry and Molecular Biology, Institute of Molecular Biology, University of Oregon, Oregon, USA,1989 – 1990
- Post Graduate Certificate in Education, Institute of Education, University of London, London, England, 1983 – 1984
- B.Sc. (Hons) Biological Science, University of East Anglia, Norwich, England, 1980 – 1983