Joep Joosten

Foto Joep Joep.Joosten[at]
+31(0)24 3616748
Lab 6.15

Unravelling the composition of membraneless organelles by proximity labeling

Cells are organized in subcompartments to streamline biochemical reactions and to facilitate spatiotemporal regulation of the biological processes that are required for life. Aside from well described membrane-encapsulated organelles such as mitochondria and the endoplasmic reticulum, numerous membraneless organelles (MLOs) exist. Many of these MLOs play crucial roles in organizing and regulating cellular processes.

Because they lack a membrane, MLOs can freely take up a wide range of RNAs and proteins. Their close link to vital cellular processes also has a downside: small mutations in certain condensate proteins have been shown to cause aberrant phase separation and aggregation, ultimately leading to degenerative diseases such as ALS and myopathy. The precise consequences of such aberrant phase separations are difficult to predict: they depend strongly on which other proteins and RNAs are present in the effected organelles.

Therefore, I am using  proximity labelling to map out the composome (the collection of all protein and RNA components) of healthy and aberrantly formed membraneless organelles. This will provide insight into which proteins are present in these healthy liquid droplets and aberrant solid aggregates. I am currently using the recently reported granules of small heat shock protein HspB2 and HspB3 as a model system.



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