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., 2024. FLIMPA: A versatile software for Fluorescence Lifetime Imaging Microscopy Phasor Analysis. bioRxiv, pp.2024-09.

LLPS and ALS Pathology

We study how liquid-liquid phase separation (LLPS) contributes to FUS misfolding and aggregation in ALS.

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.