Prof. Shulamit Michaeli of the Mina and Everard Goodman Faculty of Life Sciences and member of the Nano Medicine Center at the Institute of Nanotechnology and Advanced Materials (BINA), is an expert on silencing RNA. Michaeli designs and synthesizes RNA-protein complexes that inhibit the function of a variety of genes from human parasites to man.
Michaeli is currently pursuing a number of projects dedicated to combating parasitic diseases using RNA-silencing.
Her model systems are the trypanosomes, parasitic protozoa that cause devastating diseases such as sleeping sickness, leishmaniasis, and Chagas’ disease, affecting millions of people worldwide. Her team is investigating processes that are unique to the parasite, with the hope of finding unique targets for therapy.
Michaeli’s research group focuses on RNA molecules that participate in RNA trans-splicing unique to these parasites. They are interested in the structure and function of novel anti-sense non-coding RNAs, as well as the mechanism behind a novel RNAi silencing event discovered in their laboratory, snoRNAi, which silences nucleolar RNAs.
Recently, Michaeli’s team discovered a novel stress-induced mechanism that silences the production of mRNA by abolishing trans-splicing that leads to apoptosis. Naming the process SLS, they plan to identify chemical compounds that elicit this death pathway as potential chemotherapy.
In order to understand how the two individually transcribed RNAs associate in the spliceosome, and which small snRNAs and specific proteins are involved in this process, Michaeli’s team reconstituted the reaction in vitro.
Moreover, they recently identified a unique SL RNP (Spliced Leader Small Nuclear Ribonucleoprotein) complex that disposes of RNA if not utilized in splicing, and termed the mechanism SLD (for RNA discard). It is the first mechanism described thus far that removes defective RNA not by degradation but by sequestration and excretion from the cell via exosomes. This exosomal excretion might be used as a means of communication between these parasites within the population and with the host.
Michaeli’s group combines bioinformatics and experimental approaches to study RNomics of trypanosomes such as identifying RNA targets, which are the target of non-coding regulatory RNAs, as well as screening for novel RNAs using next-generation sequencing.
Michaeli has also parleyed her systems-based understanding of diabetes into a biotechnological breakthrough: an implantable bio-sensor – developed together with Dr. Benny Motro – that continuously measures levels of glucose in the blood, and transmits the results in real time to a monitor outside the body.
In addition, Michaeli’s team studies the mechanism of protein sorting across the ER, in particular the role of the signal recognition particles (SR), as well as unique RNA quality control mechanisms that regulate the level of non-coding RNAs.
They are also investigating nuclear RNA silencing in human cells and exploring the use of nanotechnology for gene silencing. They use a variety of methodologies including generating of transgenic parasites, knock-out, RNAi silencing, biochemical fractionation of RNA-protein complexes, microarray analysis of the transcriptome, and live cell imaging of RNA, proteins and more.
In collaboration with Prof. Jean-Paul Lellouche, Michaeli is fabricating hybrid nanoparticles in which silencing RNA is bound to the surface of various types of inorganic nanosized carriers for delivery to cancer cells. In another project, conducted together with Prof. Aharon Gedanken, Michaeli is employing microwave-based techniques to create nanoparticles from RNA itself.