Research Synopsis

The Mole lab is 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.

We are particularly interested in neurodegenerative diseases. We focus on lysosomal disorders, especially the neuronal ceroid lipofuscinoses (NCLs) or Batten disease, which are inherited neurodegenerative diseases that start in childhood. We work along the full translational pathway, studying their genetics and biology, and are developing new and much-needed therapies. Our work will help to provide new therapeutic targets for all types of neurodegeneration.

Selected Publications

Berkovic SF, et al (2019). Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features. Brain, 142(1), 59-69. doi: 10.1093/brain/awy297.

Mole SE, et al (2019). Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis. Lancet Neurol, 18(1), 107-116. doi: 10.1016/S1474-4422(18)30368-5.

kleine Holthaus SM, et al (2018). Prevention of Photoreceptor Cell Loss in a Cln6nclf Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells. Mol Ther, 26(5), 1343-1353. doi: 10.1016/j.ymthe.2018.02.027.

Danyukova T, et al (2018). Loss of CLN7 results in depletion of soluble lysosomal proteins and impaired mTOR reactivation. Hum Mol Genet, 27(10), 1711-1722. doi: 10.1093/hmg/ddy076.

Bond ME, et al (2015). A central role for TOR signalling in a yeast model for juvenile CLN3 disease. Microbial Cell, 2 (12), 466-480. doi:10.15698/mic2015.12.241

Williams RE & Mole SE (2012). New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology, 79 (2), 183-191. doi:10.1212/WNL.0b013e31825f0547

Mole SE (2011). Mutations in NCL genes. In S. E. Mole, R. E. Williams, H. H. Goebel (Eds.), The Neuronal Ceroid Lipofuscinoses (Batten Disease) (pp. 340-342). Oxford University Press.

Nosková L, et al (2011). Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. Am J Hum Genet, 89 (2), 241-252. doi:10.1016/j.ajhg.2011.07.003

Kitzmüller C, et al (2008). A function retained by the common mutant CLN3 protein is responsible for the late onset of juvenile neuronal ceroid lipofuscinosis (JNCL). Human Molecular Genetics, 17, 303-312. doi:10.1093/hmg/ddm306

About the lab

Funders

Wellcome Trust

Medical Research Council

EU H2020

Batten Disease Family Association

Biomarin

Batten Disease Support and Research Association USA

Children's Brain Disease Foundation USA

Research Themes

Signalling pathways, Membrane trafficking, Disease

Technology

Light microscopy, Translational research, Bioinformatics, Electron microscopy, Microbiology

People

Elisa Tinelli (Postdoctoral Research Associate)

Sophia kleine Holthaus (Postdoctoral Research Associate)

Mikel Aristorena (Postdoctoral Research Associate)

Christopher Minnis (PhD Student)

Yaxuan Lyu (PhD Student)

Carlota Miranda Sole (ERASMUS Student)

Collaborators

Paul Gissen (LMCB, UK)
Robin Ketteler (LMCB, UK)
Robin Ali (UCL, UK)
Ahad Rahim (UCL, UK)
Tris McKay (Manchester Metropolitan University, UK)
Thomas Wishart (Roslin Institute, UK)
Emyr Lloyd-Evans (Cardiff University, UK)
Heather Band (Batten Disease Family Association, UK)
Angela Schulz (University Medical Centre Hamburg-Eppendorf, Germany)
Torbjorn Lundstedt (AcureOmics, Sweden)
Maija Dambrova (Latvian Institute of Organic Synthesis, Latvia)
Diego Medina (Telethon Insitute of Genetics and Medicine, Italy)
Juan Bolanos (University of Salamanca, Spain)
Jan Kehr (Pronexus Analytics, Sweden)
Claire Russell (Royal Veterinary College, UK)
Thomas Kirkegaard (Orphazyme, Denmark)
Jonathan Cooper (Los Angeles Biomedical Research Institute, USA)
Marc Masa (LEITAT Technological Center, Spain)