Sander Granneman

The role of non-coding RNAs and RNA-binding proteins in regulating gene expression during adaptive responses in microbes.

Sander Granneman is a Dutch Professor (Chair) in RNA Biochemistry at the School of Biological Sciences, University of Edinburgh. He studied Molecular Biology at the University of Amsterdam and completed his PhD in autoimmune diseases in Nijmegen, the Netherlands. After a postdoc at Yale University studying the assembly of large macromolecular complexes in yeast, Sander continued his research in David Tollervey's lab, where he developed innovative methods for globally mapping protein-RNA interactions and collaborated with UVO3 to develop improved crosslinking equipment for capturing these interactions.

portrait photo of Sander Granneman
Sander Granneman

Funded by a Wellcome Trust Career Development Fellowship, Sander established his independent research group at the Centre for Systems Biology in Edinburgh in 2011. During this period, he developed new high-throughput approaches for probing the structure of RNA in living cells and, with his collaborators, contributed to the development of machine learning pipelines to mine the data. He subsequently received an MRC Senior Research Fellowship to advance his work on RNA-binding proteins and non-coding RNAs in pathogenic bacteria. 

Sander's research group was the first to unravel the RNA-binding proteome and RNA-RNA interactomes in methicillin-resistant Staphylococcus aureus (MRSA), leading to the discovery of many new RNA-binding proteins and revealing RNA-RNA interactions that contribute to MRSA virulence and antibiotic resistance. These findings paved the way for developing therapeutic strategies against antibiotic-resistant infections.

Dina Nahas, Sara Pintar, Mehak Chauhan, Hong Duong-Ngo and Gabriele Bagusinskaite.


The Granneman lab studies the role of non-coding RNAs and RNA-binding proteins in regulating gene expression during adaptive responses in microbes. Many microorganisms, particularly human pathogens, have evolved sophisticated mechanisms to rapidly adapt to environmental stresses, such as changes in host temperature and nutrient availability. This enables them to efficiently maintain cellular homeostasis even in hostile environments.

Our goal is to gain mechanistic insights into the regulatory strategies these organisms use to adapt to stress through highly interdisciplinary approaches, including high-throughput sequencing, proteomics, structural biology, drug discovery, protein-RNA biochemistry, and the development of AI/ML tools for analyzing the resulting data. We use brewer's yeast and clinically relevant methicillin-resistant Staphylococcus aureus as model organisms.

The ultimate goal of our research is to obtain detailed mechanistic insights into how organisms regulate gene expression during rapid adaptive responses and to exploit these findings in the fight against infections.


Diagram of CRAC RBPome process

Mediati DG, Wong JL, Gao W, McKellar S, Pang CNI, Wu S, Wu W, Sy B, Monk IR, Biazik JM, Wilkins MR, Howden BP, Stinear TP, Granneman S, Tree JJ. RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3'UTR required for intermediate vancomycin resistance. 
Nat Commun. 2022 Jun 22;13(1):3558. doi: 10.1038/s41467-022-31177-8.

McKellar SW, Ivanova I, Arede P, Zapf RL, Mercier N, Chu LC, Mediati DG, Pickering AC, Briaud P, Foster RG, Kudla G, Fitzgerald JR, Caldelari I, Carroll RK, Tree JJ, Granneman S. RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression. Nature Commun. 2022 Jun 22;13(1):3560. doi: 10.1038/s41467-022-31173-y. PMID: 35732654; PMCID:PMC9217828.

Chu LC, Arede P, Li W, Urdaneta EC, Ivanova I, McKellar SW, Wills JC, Fröhlich T, von Kriegsheim A, Beckmann BM, Granneman S. The RNA-bound proteome of MRSA reveals post-transcriptional roles for helix-turn-helix DNA-binding and Rossmann-fold proteins. Nature Commun. 2022 May 24;13(1):2883. doi:10.1038/s41467-022-30553-8. PMID: 35610211; PMCID: PMC9130240.

van Nues R, Schweikert G, de Leau E, Selega A, Langford A, Franklin R, Iosub I, Wadsworth P, Sanguinetti G, Granneman S. Kinetic CRAC uncovers a role for Nab3 in determining gene expression profiles during stress. Nature Commun. 2017 Apr 11;8(1):12. doi: 10.1038/s41467-017-00025-5. PMID: 28400552; PMCID: PMC5432031.

Selega A, Sirocchi C, Iosub I, Granneman S, Sanguinetti G. Robust statistical modeling improves sensitivity of high-throughput RNA structure probing experiments. Nature Methods. 2017 Jan;14(1):83-89. doi: 10.1038/nmeth.4068. Epub 2016 Nov 7. PMID: 27819660.

 


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