By Ozlem Tastan Bishop
The infectious disease burden in Africa is very high, particularly for tuberculosis (TB), malaria and HIV/AIDS. In 2018, nearly a quarter (24%) of TB cases in the world were in Africa. The region accounted for 93% of malaria cases. The continent also bears the brunt of the HIV epidemic: 20.6 million of the 37.9 million people living with HIV are in eastern and southern Africa.
To solve disease problems, scientists in Africa need to push boundaries and think outside the box. And I believe that we can do so.
My research is based on using computers to understand biological problems at the protein level. This is part of bioinformatics, a young but broad discipline. Its applications are wide and range from understanding the genome sequence of any organism to drug discovery.
My research goal is to understand the mechanisms, at a molecular level, of diseases relevant to Africa – and to find solutions. Under a grant from Grand Challenges Africa: Drug Discovery Programme we would like to tackle two separate but interlinked biological problems. These are: to understand drug resistance mechanisms; and to find alternative drug targeting sites to design novel drugs.
Our research is outside the box of conventional drug discovery as it asks the following question: what are the drug resistance mechanisms – at a molecular level – behind TB and malarial drugs?
In previous research, we made a novel and significant finding. We were able to identify the resistance mechanism in an HIV drug target protein. We did this by observing a change of behaviour in the protein against eight currently used drugs.
The findings are the first step to designing better drugs against HIV because they gave us novel drug targeting sites in the protein. Now we would like to apply our approaches to understand TB and malarial drug resistance. From there we hope to identify alternative drug targeting sites.
The problem
Let’s look at the problem from the perspective of infectious diseases. Many drugs target the functional site of a protein of a pathogen (the microorganism that causes disease). We call them active site drugs. They aim to block the function of the protein, hence the pathogen’s life cycle. These drugs have been successfully used in therapies, for instance, to reduce viral loads in HIV patients to undetectable levels.
