Linking ER function with lysosomal dysfunction

Sara Mole (primary)
Institute of Child Health (lab in MRC LMCB)
Sandip Patel (secondary)
Department of Cell and Developmental Biology


The activity of certain genes is vital to cellular health as exemplified by familial forms of disease, yet the function of many of these genes is still not delineated. The aim of this study is to advance understanding of the molecular mechanisms linking mutations in resident proteins of the endoplasmic reticulum to dysfunction of lysosomes. The project will combine expertise in disease modelling and cellular signalling to study the functional coupling between CLN6, a transmembrane protein of the ER, and neuronal ceroid lipofuscinosis, a lysosomal storage disease.


1 Mole SE, Cotman SL. Genetics of the neuronal ceroid lipofuscinoses (Batten disease). Biochim Biophys Acta. 2015 Oct;1852(10 Pt B):2237-41. doi: 10.1016/j.bbadis.2015.05.011. Review.
2 Marotta D, Tinelli E, Mole SE. NCLs and ER: A stressful relationship. Biochim Biophys Acta. 2017 Apr 6;1863(6):1273-1281. doi: 10.1016/j.bbadis.2017.04.003. Review.
3 Penny CJ, Kilpatrick BS, Eden ER, Patel S. Coupling acidic organelles with the ER through Ca²⁺ microdomains at membrane contact sites. Cell Calcium. 2015 Oct;58(4):387-96. doi: 10.1016/j.ceca.2015.03.006. Review
4 Kilpatrick BS, Eden ER, Hockey LN, Yates E, Futter CE, Patel S. An Endosomal NAADP-Sensitive Two-Pore Ca2+ Channel Regulates ER-Endosome Membrane Contact Sites to Control Growth Factor Signaling.Cell Rep. 2017 Feb 14;18(7):1636-1645. doi: 10.1016/j.celrep.2017.01.052.
5 Kleine Holthaus SM, Ribeiro J, Abelleira-Hervas L, Pearson RA, Duran Y, Georgiadis A, Sampson RD, Rizzi M, Hoke J, Maswood R, Azam S, Luhmann UFO, Smith AJ, Mole SE, Ali RR. Prevention of Photoreceptor Cell Loss in a Cln6nclf Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells. Mol Ther. 2018 May 2;26(5):1343-1353. doi: 10.1016/j.ymthe.2018.02.027.

Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyNeurobiology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsGeneticsImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular Biology