Biomolecular condensates
In the last decade it has become increasingly clear that cells harbor countless condensates—membraneless assemblies that compartmentalize and organize biochemistry in time and space. We have been interested in how regulated condensation is encoded in protein sequence and how this process relates to biological function and fitness. Moreover, since aberrant condensation is increasingly implicated in human disease, a deeper understanding of the molecular rules and regulatory principles will highlight new therapeutic approaches.
By combining evolutionary analyses with synthetic biology approaches, and in vitro and cellular condensation assays, we are slowly uncovering the molecular grammar that dictates condensation behavior.
Selected publications
Field S, Dorone Y, Dwyer WP, Cox JA, Raba D, Froehlich J, Blea M, Carmo OMS, Wallace IS, Hastings R, Boeynaems S, Rhee SY. Arabidopsis thaliana RHAMNOSE 1 condensate formation drives UDP-rhamnose synthesis. BioRxiv 2024.
Boeynaems S#, Dorone Y, Zhuang Y, Shabardina V, Huang G, Anca M, Kim G, Sanyal A, Sen N-E, Griffith D, Docampo R, Lasker K, Ruiz-Trillo I, Auburger G, Holehouse AS, Kabashi E, Lin Y, Gitler AD#. Poly(A)-binding protein is an ataxin-2 chaperone that regulates biomolecular condensates. Molecular Cell 2023. co-corresponding
Lasker K*, Boeynaems S*, Lam V, Scholl D, Stainton E, Briner A, Jacquemyn M, Daelemans D, Deniz A, Villa E, Holehouse AS, Gitler AD, Shapiro L. The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems. Nature Communications 2022, vol. 13, 5643. co-first
Dorone Y*, Boeynaems S*, Jin B, Bossi F, Flores E, Lazarus E, Michiels E, De Decker M, Baatsen P, Holehouse AS, Sukenik S, Gitler AD, Rhee SY. A prion-like protein regulator of seed germination undergoes hydration-dependent phase separation. Cell 2021, vol. 184(16), p. 4284-4298. co-first
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Fumagalli F*, Young FL*, Boeynaems S*, De Decker M, Mehta A, Swijsen A, Fazal R, Guo W, Moisse M, Beckers J, Dedeene L, Bhuvaneish TS, Vandoorne T, Madan V, van Blitterswijk M, Raitcheva D, McCampbell A, Poesen K, Gitler AD, Koch P, Vanden Berghe P, Thal DR, Verfaillie C, Chandran S, Van Den Bosch L, Bullock S, Van Damme P. C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility. Science Advances 2021, vol. 7(15), eabg3013. co-first
Hasting RL and Boeynaems S#. Designer condensates: a toolkit for the biomolecular architect. Journal of Molecular Biology 2021, vol. 433(12), 166837. corresponding
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Gittings L, Boeynaems S, Lightwood D, Clargo A, Topia S, Nakayama L, Troakes C, Mann D, Gitler AD, Lashley T, Isaacs A. Symmetric dimethylation of poly-GR correlates with disease duration in C9orf72 FTLD and ALS and reduces poly-GR phase separation and toxicity. Acta Neuropathologica, vol. 139, p. 407–410.
Boeynaems S, Holehouse AS, Weinhardt V, Kovacs D, Van Lindt J, Larabell C, Van Den Bosch L, Das R, Tompa P, Pappu RV, Gitler AD. Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties. PNAS, vol. 116(16), p. 7889-7898. co-corresponding
Bogaert E*, Boeynaems S*, Kato M, Guo L, Caulfield TR, Steyaert S, Scheveneels W, Wilmans N, Haeck W, Hersmus N, Schymkowitz S, Rousseau F, Shorter J, Callaerts P, Robberecht W, Van Damme P, Van Den Bosch L. Molecular dissection of FUS points at synergistic effect of low-complexity domains in toxicity. Cell Reports, vol. 24(3), p. 529-537. co-first, co-corresponding
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Boeynaems S, Alberti S, Fawzi NL, Mittag T, Polymenidou M, Rousseau F, Schymkowitz J, Shorter J, Wolozin B, Van Den Bosch L, Tompa T, Fuxreiter M. Protein phase separation: a new phase in cell biology. Trends in Cell Biology, vol. 28(6), p. 420–435. co-corresponding
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Boeynaems S, Bogaert E, Kovacs D, Konijnenberg A, Timmerman E, Volkov A, Guharoy M, De Decker M, Jaspers T, Ryan VH, Janke AM, Baatsen P, Vercruysse T, Kolaitis RM, Daelemans D, Taylor JP, Kedersha N, Anderson P, Impens F, Sobott F, Schymkowitz J, Rousseau F, Fawzi NL, Robberecht W, Van Damme P, Tompa P, Van Den Bosch L. Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics. Molecular Cell, vol. 65(6), p. 1044-1055.
featured on the cover