Full Member, IDM; Honorary Research Professor, Division of Chemical Systems & Synthetic Biology; Faculty of Health Sciences, University of Cape Town
Adjunct Faculty, Institute for Molecular Medicine, Lisbon Portugal
Visiting Faculty, Harvard University Chan School of Public Health
Novel imaging technologies including super-resolution imaging and automated fluorescent microscopy have dramatically altered the way molecular processes are investigated by cell biologists. Our laboratory uses quantitative imaging to “eavesdrop” on cellular events at the single molecule scale. Our research has focused on understanding how RNA biology and nuclear architecture influence some of the most fundamental processes in cell biology. My graduate career began with David Ho and then with Fred R. Kramer and Sanjay Tyagi (The Rockefeller University and then at New York University School of Medicine). I was then awarded a United States National Science Foundation Postdoctoral Fellowship to work in the laboratory of Ulf Nehrbass at the Institut Pasteur in Paris, France. In late 2008 I moved my laboratory to South Africa.
Highly reduced, our core scientific questions to which we apply a myriad of tools are: Understanding the fundamental roles of genome architecture and RNA in spatial control of gene expression. We have harnessed the use of pathogens to decrypt this process. Several seminal contributions have emerged from our research including: The development of super-resolution microscopy tools (QuickPALM, NatureMethods , Journal of Cell Biology); the use of such tools to study higher order signalosomes (Nature Communications); and the causal nature of chromosomal contacts or “gene kissing” on transcription (Cell, Nucleus, Transcription); that pathogens utilize the “dark matter of the genome” (mirRNAs and lncRNAs) to direct host transcriptional and translational programs to avoid apoptosis (Frontiers); and systems biology approaches (DYPFISH) revealing RNA are spatially localized at sub-cellular scale.
Samantha Barichievy, Jerolen Naidoo, Mikaël Boullé, Janine Scholefield, Suraj P. Parihar, Anna K. Coussens, Frank Brombacher, Alex Sigal and Musa M. Mhlanga. Viral Apoptosis Evasion via the MAPK Pathway by Use of a Host Long Noncoding RNA. Front. Cell. Infect. Microbiol. 8(2018).
Fanucchi S, Mhlanga MM. Lnc-ing Trained Immunity to Chromatin Architecture.FrontCell Dev Biol. 2019 Jan 24;7:2.
Stephanie Fanucchi, Ezio T. Fok, Emiliano Dalla, Youtaro Shibayama, Kathleen Börner, Erin Y. Chang, Stoyan Stoychev, Maxim Imakaev, Dirk Grimm, Kevin C. Wang, Guoliang Li, Wing-Kin Sung & Musa M. Mhlanga. Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments. Nature genetics 51.1 (2019): 138
Anca F. Savulescu, Robyn Brackin, Emmanuel Bouilhol, Benjamin Dartigues, Jonathan H. Warrell, Mafalda R. Pimentel, Stephane Dallongeville, Jan Schmoranzer, Jean-Christophe Olivo-Marin, Edgar R. Gomes, Macha Nikolski, Musa M. Mhlanga. DypFISH: Dynamic Patterned FISH to Interrogate RNA and Protein Spatial and Temporal Subcellular Distribution. Available at SSRN 3323373 (2019).
Timothy J de Wet, Irene Gobe, Musa M Mhlanga, Digby F Warner. CRISPRi-Seq for the Identification and Characterisation of Essential Mycobacterial Genes and Transcriptional Units. BioRxiv (2018): 358275.
Janine Scholefield, Ricardo Henriques, Anca F. Savulescu, Elisabeth Fontan, Alix Boucharlat, Emmanuel Laplantine, Asma Smahi, Alain Israel, Fabrice Agou & Musa M. Mhlanga (2016). Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti. Nature communications 7 (2016): 12629.
Samantha Barichievy, Jerolen Naidoo, Musa M. Mhlanga (2015). Non-coding RNAs and HIV: viral manipulation of host dark matter to shape the cellular environment. Frontiers in Genetics 6:108.
Tarantino Nadine, Tinevez Jean-Yves, Crowell Elizabeth Faris, Boisson Bertrand, Henriques Ricardo, Mhlanga Musa, Agou Fabrice, Israël Alain, Laplantine Emmanuel (2014). TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supra-molecular structures. Journal of Cell Biology 204(2):231-245.
Fanucchi Stephanie, Shibayama Youtaro, Burd Shaun, Weinberg Marc S, Mhlanga Musa M. (2013). Chromosomal contact permits transcription between co-regulated genes. Cell 155 (3):606-620.
Meliopoulos VA, Andersen LE, Birrer KF, Simpson KJ, Lowenthal JW, Bean AG, Stambas J, Stewart CR, Tompkins SM, van Beusechem VW, Fraser I, Mhlanga M, Barichievy S, Smith Q, Leake D, Karpilow J, Buck A, Jona G, Tripp RA. (2012). Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. FASEB (4):1372-86.
Henriques R, Griffiths C, Rego EH and Mhlanga MM (2011). PALM and STORM: unlocking live-cell super-resolution. Biopolymers 95(5):322-31.
Henriques R, Lelek M, Fornasiero EF, Valtorta F, Zimmer C, Mhlanga MM (2010). QuickPALM: 3D real-time photoactivation nanoscopy image processing in ImageJ. Nature Methods 7(5):339-40.
Room N2.03, Wernher & Beit North
Institute of Infectious Disease and Molecular Medicine
Faculty of Health Sciences
University of Cape Town