Dr Francisco Olmo
BSc MSc PhD
I graduated in Biochemistry and Biology in the University of Granada (Spain) in 2009. During this time I became interested in Parasitology, and I started as a fellow in the Department of Parasitology during my last year of degree, where I combined basic research and teaching in practice sessions. I also completed my MSc in Biotechnology (2010) in the University of Granada with a short stay in the Department of Microbiology and Immunology in the University of Adelaide, (Prof. Shaun McColl’ Lab). Following this I started a PhD in Clinical Medicine and Public Health in the University of Granada (Prof. Manuel Sánchez-Moreno and Clotilde Marín) where I focused on the application of supramolecular chemistry in the search for active compounds against Trypanosoma cruzi infection in mouse model. During my PhD I enjoyed two research stays in different labs, first in Prof. Luise Krauth-Siegel (University of Heidelberg, Germany) and the second in Prof. John Kelly (London School of Hygiene and Tropical Medicine, UK). After my PhD in March 2015 I did a short postdoc research stay in the Prof. Rick Tarleton (University of Georgia, USA).
The Kelly lab has developed an enhanced non-invasive bioluminescence imaging system, which allows the distribution and burden of low levels of parasitemia in murine models to be established during chronic infections. Using this technology, the therapeutic effectiveness of anti-parasitic drugs can be readily assessed by tracking post-treatment parasitemia in real time. The host laboratory is part of a DNDi-sponsored Lead Optimisation Consortium for Chagas disease, which brings together expertise in medicinal chemistry, PK/PD, and high-throughput in vitro screening, to design and select compounds to be assessed using the in vivo imaging model. The group also contribute to the GSK Chagas disease drug development pipeline by providing an in vivo screening service. Added value can also be built into the lead optimisation process by target identification and discovery of potential resistance mechanisms. The availability at LSHTM of cutting edge genetic technology applicable to trypanosomes (Kelly and Alsford groups), provide a framework for achieving this.
My work as research assistant in the laboratory of Professor Kelly is awarded with a grant from the Tres Cantos Open Lab Foundation. The aim of the project will be to add value to the lead optimization process by identifying the intra-parasite targets of compounds showing most therapeutic promise, deciphering their mechanisms of action, and assessing the potential for resistance. Identification of genes involved in resistance to novel compounds from the HTS formerly prosecuted at GSK will be approached through complementary high-throughput genetic methodologies, such as RITseq in T. brucei, CRISPR/cas9 in T. cruzi and construction of a T. cruzi cosmid over-expression library. The set of genetic constructs will be screened against GSK Chagas Box in order to assess the modes of action and/or resistance mechanisms of lead compounds in T. cruzi. Furthermore, in vivo screening can be undertaken to assess physiological relevance