Neglected tropical diseases are a collection of 20 infectious diseases that impact over 1/6^th of the world’s people.² Of these the parasitic infection leishmaniasis has one of the highest disease burdens.³ Endemic to most parts of the developing world, there are estimated to be > 1 million new infections annually, with those affected by poverty, malnutrition, displacement, and poor housing being most at risk.^{1, 4} In many communities the skin lesions and severe facial scarring that result from the disease bring profound social stigma.⁵ Current treatments are inadequate; being highly toxic, requiring painful daily injections, having low efficacy and are expensive.⁶ Recently, increasing resistance to the few available medications has been observed.⁷ Thus, it is clear new, safe, topical or oral, well tolerated, and affordable treatments are needed.⁷ However, low commercial return means that it receives little attention from pharmaceutical companies.

The long term objective of the research is to advance our understanding of the parasite leishmania and ultimately develop a new validated drug target with associated drug lead, which has the potential to serve as a novel anti-leishmania compound.  It is an exercise in chemical proteomics, exploring how to develop therapies by looking at how well different chemicals inhibit the functioning of kinases, which are key enzymes involved in cell signalling. The main reason I find this project so exciting is the huge potential social impact it could have: transforming the lives of millions of the world’s most vulnerable people affected by this horrific disease each year. 

The specific aims of the project are as follows:

1. Synthesise a novel chemical probe using standard synthetic techniques developed by my academic supervisor and his lab group.
2. Apply the principals of chemical proteomics to identify potential new drug targets in the leishmania parasite – specifically on kinase molecules.
3. Screen a library of compounds in competitive labelling experiments against the chemical probe using the SDS-PAGE technique.

References:

• 1.            E. TorresGuerrero, M. Quintanilla-Cedillo, J. Ruiz-Esmenjaud and R. Arenas, F1000Research,                            2017, 6.
• 2.            D. A. ÁlvarezHernández, L. Rivero-Zambrano, L. A. Martínez-Juárez and R. García-Rodríguez-                        Arana, Ther Adv Infect Dis, 2020, 7, 2049936120966449.
• 3.            C. J. Scheufele, R. L. Giesey and G. R. Delost, J Am Acad Dermatol, 2021, 84, 12031205.
• 4.            J. Alvar, S. Yactayo and C. Bern, Trends Parasitol, 2006, 22, 552557.
• 5.            I. Bennis, V. De Brouwere, Z. Belrhiti, H. Sahibi and M. Boelaert, BMC Public Health, 2018, 18,                         358.
• 6.            eBioMedicine, eBioMedicine, 2023, 87, 104440.
• 7.            S. L. Croft, S. Sundar and A. H. Fairlamb, Clin Microbiol Rev, 2006, 19, 111126.