Amyotrophic Lateral Sclerosis (ALS)
FUS in iPSCs
We investigate FUS mutations in iPSC-derived neurons, exploring their role in RNA metabolism, splicing, and neurotoxicity in ALS.
FUS Aggregation in Worm Models & FLIM data analysis
Using FLIM, we quantify FUS aggregation in C. elegans, providing a live-model system to track ALS progression. To facilitate the FLIM data analysis we have developed FLIMPA, a user-friendly phasor plot analysis software.
Murakami, T., Qamar, S., Lin, J.Q., Schierle, G.S.K., Rees, E., Miyashita, A., Costa, A.R., Dodd, R.B., Chan, F.T., Michel, C.H. and Kronenberg-Versteeg, D., 2015. ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function. Neuron, 88(4), pp.678-690.
Kapsiani, S., Läubli, N.F., Ward, E.N., Shehata, M., Kaminski, C.F. and Kaminski Schierle, G.S., 2025. FLIMPA: A versatile software for Fluorescence Lifetime Imaging Microscopy Phasor Analysis. Analytical Chemistry.
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​Resnick, S.J., Qamar, S., Krishna, P., Korobeynikov, V., Ausserwoger, H., Miller, A., Esposito, P., Varela, J.A., Sheng, J., Huang, L.H. and Nixon-Abell, J., 2025. Multiplex neurodegeneration proteotoxicity platform reveals DNAJB6 promotes non-toxic FUS condensate gelation and inhibits neurotoxicity. Nature Communications, 16(1), p.10285.
LLPS and ALS Pathology
We study how liquid-liquid phase separation (LLPS) contributes to FUS misfolding and aggregation in ALS.
Fischer, C.M., Toprakcioglu, Z., de Csilléry, E., Kaminski Schierle, G.S. and Knowles, T.P., 2025. The Liquid State of RIM1α and RBP Condensates is Maintained by Lipids. ACS nano.
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Chung, C.W., Zhou, A.J., Mela, I., Stephens, A.D., Miyashita, A., St George-Hyslop, P.H., Kaminski, C.F., Knowles, T.P. and Kaminski Schierle, G.S., 2022. Intracellular FUS protein accumulation leads to cytoskeletal, organelle and cellular homeostasis perturbations. bioRxiv, pp.2022-10.
Qamar, S., Wang, G., Randle, S.J., Ruggeri, F.S., Varela, J.A., Lin, J.Q., Phillips, E.C., Miyashita, A., Williams, D., Ströhl, F. and Meadows, W., 2018. FUS phase separation is modulated by a molecular chaperone and methylation of arginine cation-π interactions. Cell, 173(3), pp.720-734.
Collaborations
We work with leading ALS researchers and electrophysiologists, including Prof. Peter St. George-Hyslop (Columbia University, US), Prof. András Lakatos (University of Cambridge, UK), and Prof. Ole Paulsen (University of Cambridge, UK), to develop targeted therapies.