Sarah Mizielinska Group
My research group investigates the molecular and cellular mechanisms involved in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), with the aim of better understanding the causes of dementia and neurodegeneration and ultimately providing new and effective targets for disease therapy.
Our research explores how nucleocytoplasmic transport is affected in FTD/ALS at the single molecule level, and how this links to common disease pathologies. Studies focus on disease-associated proteins containing low complexity domains, such as the toxic dipeptide repeat proteins identified pathologically in individuals carrying C9orf72 mutations or TDP-43. This multidisciplinary work utilises super-resolution microscopy to investigate the dynamics of single molecule cargo through the nuclear pore combined with biophysical studies to study phase transitioning of nuclear pore selection barriers to unveil unique disease pathomechanisms often overlooked from bulk endpoint analyses.
We have a keen interest in developing new methodologies and quantitative analyses, particularly in novel and super-resolution imaging technologies.
This programme is part of the UK DRI at King’s College London.
Bidirectional nucleolar dysfunction in C9orf72 frontotemporal lobar degeneration.
Mizielinska S, Ridler CE, Balendra R, Thoeng A, Woodling NS, Grässer FA, Plagnol V, Lashley T, Partridge L, Isaacs AM.
Acta Neuropathol Commun. 2017 Apr 18;5(1):29.
C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins.
Mizielinska S, Grönke S, Niccoli T, Ridler CE, Clayton EL, Devoy A, Moens T, Norona FE, Woollacott IOC, Pietrzyk J, Cleverley K, Nicoll AJ, Pickering-Brown S, Dols J, Cabecinha M, Hendrich O, Fratta P, Fisher EMC, Partridge L, Isaacs AM.
Science. 2014 Sep 5;345(6201):1192-1194.
C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci.
Mizielinska S, Lashley T, Norona FE, Clayton EL, Ridler CE, Fratta P, Isaacs AM.
Acta Neuropathol. 2013 Dec;126(6):845-57.