Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at http://www.ucl.ac.uk/finance/research/post_award/post_award_contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
 More search options
Dr Sara Mole
MRC Laboratory for Molecular Cell Biology
  • Reader in Molecular Cell Biology
  • ICH Genetics & Genomic Medicine Prog
  • Institute of Child Health
  • Faculty of Pop Health Sciences
Research Themes
Research Summary

I am interested in disease caused by genetic changes and how study of these mutations and their effects can reveal important and complex aspects of cell biology that may otherwise be beyond current appreciation. I make use of model systems.

My main research interest is the molecular genetics and biology of the neuronal ceroid lipofuscinoses (NCL) or Batten disease, a group of inherited neurodegenerative diseases that affect lysosome homeostasis. This group of diseases are rare but understanding their biology may open new avenues for understanding more common neurodegenerative conditions as well as the basic biology of neurons and associated cells. When I began this work none of the genes had been identified so my initial research strategy was one of genetic linkage, eventually progressing to the molecular and cell biology of the genes I identified. Fourteen genes have now been identified. I work closely with others whose aim is to identify the remaining NCL disease genes by pooling resources and expertise. I curate the NCL Resource web site, which acts as a gateway for Batten disease and includes the Mutation Database which I maintain on behalf of the international NCL community (http://www.ucl.ac.uk/ncl). 

Within my own laboratory I have a particular interest in the biology of CLN3, a highly conserved gene, and of CLN6 and CLN8, vertebrate genes, whose functions remain elusive. We currently use mammalian systems and the model organism Schizosaccharomyces pombe and have studied their location, topology, trafficking signals, interacting partners and effect on cells of complete loss of function. The function of CLN3 is complex and more important than was expected, and the fission yeast model system has recently revealed novel aspects of its function including a role in polarisation of lipid domains and F-actin, and trafficking, as well as effects on vacuole homeostasis, that can be explained by a role upstream of the lysosome. These effects also translate into mammalian defects, revealed by RNAi. Significantly we discovered that an intragenic deletion of CLN3 shared by most patients with juvenile NCL does not completely abolish CLN3 function, which has important implications for future therapy development. We are using various screening strategies to identify genes and small molecules that restore defects associated with loss of CLN3 function. We are currently exploring the challenges of developing a therapy that targets the visual loss in NCL since this would significantly improve the quality of life of affected children, with the ultimate target being the brain.

Recently the potential of fission yeast as a model system for mammalian cell biology that is surprisingly under exploited has allowed me to develop a system to study membrane retrieval from the vacuole, a process that has escaped previous attempts to completely decipher and which may be similar to other intracellular membrane budding events. This approach has already shown the requirement for several genes that also underlie disease and promises to reveal numerous further genes involved in this process.

Keywords: Brain, Dementia, Epilepsy, Genetics, Macula, Modelling, Neurodegeneration, Neuron, Neuroscience, Vision

Conditions: Batten disease, Batten's disease, Neurodegenerative diseases

Methods: Bioinformatic analysis, Cell culture, Confocal microscopy, Electron Microscopy, Enzyme assays, Genetic manipulation (including knockout/knockin) , Genetic screens, Genomic analyses, Light microscopic techniques, Linkage, Mapping and positional cloning, Protein transport/localisation, Recombinant protein expression, Time-lapse imaging, Other

01-OCT-1997 – 30-SEP-2004 Senior Lecturer in Molecular Genetics Paediatrics and Child Health UCL, United Kingdom
01-OCT-1992 – 30-SEP-1997 Lecturer in Molecular Genetics Paediatrics UCL, United Kingdom
Academic Background
1987 MA Master of Arts – Natural Sciences University of Cambridge
1986 PhD Doctor of Philosophy – Biochemistry Imperial College of Science, Technology and Medicine
1983 BA Hons Bachelor of Arts (Honours) – Natural Sciences University of Cambridge
Please report any queries concerning the data shown on this page to https://www.ucl.ac.uk/hr/helpdesk/helpdesk_web_form.php
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by