In biology several important processes occur at spatial dimensions currently beyond the reaches of conventional light microscopy. Our laboratory is concerned with those biological questions related to gene expression. As such the study of RNA transcription, metabolism and transport as well as it’s relation with dynamic compartmentalized multi-molecular complexes in the eukaryotic cell nucleus remain well outside the resolution of most optical microscopy techniques. The direct observation of these events at the single molecule level, is currently the subject of intense research. Intrinsic to RNA transcription are modifications to the nuclear architecture and the dynamic repositioning of chromosomal loci, as well as the interplay of several ribonucleic proteins (RNPs). These events remain opaque at the single RNA transcript level, and questions such as the timing and spatial position of interactions of these RNPs with RNA, the number of genes targeted in the transcriptional process at a single spatial location, the splicing and the export of RNA, remain unresolved. Understanding and visualizing these processes has implications not only for our understanding of basic biology, but extends to mechanisms in development and disease. Through the use of novel nucleic acid based probes (molecular beacons) for the detection of mRNA in living cells, we have recently extended these approaches to the imaging of gene expression and RNA transport in living cells.

 

Musa Mhlanga
PhD (2003) in Cell Biology from the New York University School of Medicine, USA
Postdoctoral research at Institut Pasteur, France
Group Leader at IMM since 2008

Kostrikis, L. G., Tyagi, S., Mhlanga, M. M., Ho, D. D., and Kramer, F. R. (1998). Spectral genotyping of human alleles. Science 279, 1228-1229.
 
Mhlanga, M. M., and Malmberg, L. (2001). Using molecular beacons to detect singlenucleotide polymorphisms with real-time PCR. Methods 25, 463-471.
 
Bratu, D. P., Cha, B. J., Mhlanga, M. M., Kramer, F. R., and Tyagi, S. (2003). Visualizing the distribution and transport of mRNAs in living cells. Proceedings of the National Academy of Sciences of the U.S.A., 100, 13308- 13313.
 
Mhlanga, M. M., Vargas, D. Y., Fung, C. W., Kramer, F. R., and Tyagi, S. (2005). tRNA-linked molecular beacons for imaging mRNAs in the cytoplasm of living cells. Nucleic Acids Research, 33, 1902-1912.
 
Mhlanga, M. M., and Tyagi, S. (2006). Using tRNA linked molecular beacons to image cytoplasmic mRNAs in live cells. Nature Protocols, 1, 1392- 1398.
 
Ghislain Cabal, Jost Enninga and Musa M. Mhlanga (2007) Single molecule tracking of mRNA and proteins. Book Chapter in ‘Imaging Cellular and Molecular Biological Function’ (Springer).