*Divya Venkatesh  is a Gates Cambridge Scholar doing a PhD in Pathology. Picture credit: Wiki Commons and Adrian Custer.
Last week, Bill Gates called for the world to step up the fight against 'neglected tropical diseases' such as sleeping sickness, schistosomiasis, trachoma and several others that collectively cause as much damage as HIV, malaria or tuberculosis.
The current R&D and intellectual property systems provide no incentives to pharmaceutical companies to develop and deliver drugs to those affected by these diseases. Little-known and poorly understood internationally, they are ancient diseases that have plagued humanity for centuries and still affect nearly one billion people today - people who largely lack political voice, live in remote areas and are extremely poor.
I was initially attracted to studying trypanosomes, the single-celled parasites that cause sleeping sickness, due to the sheer audacity that they seem to show in the human host. Trypanosomes remain in the bloodstream where they are exposed to the full force of our immune response, but manage to evade it by changing their surface composition using a rapid and efficient transport system.
They then manage to enter the central nervous system and start to cause the neurological symptoms that give sleeping sickness its name: sleep cycles are disrupted, there is lack of muscle coordination etc, eventually resulting in death unless treated. Drugs to treat this second stage of the disease have been very hard to develop and treatment regimens are complicated and require hospital infrastructure, which is scarce.
So it's been great to see progress in the last few years with The Bill and Melinda Gates Foundation leading the drive to increase investment into drug delivery and Research & Development. And it's particularly heartening to see that the new oral treatment Fexinidazole,which is much easier to deliver, has progressed to phase II trials.
More research needed
On the flip side - this is only the second treatment that has been developed in the past 25 years - the other one being NECT, a combination treatment of drugs already in use: intravenous eflornithine and oral nifurtimox. And considering that only about 48% of drugs progress from phase II to phase III and there are increasing incidents of drug resistance in trypanosomes, we need to develop more candidates.
Fexinidazole was developed and tested in the 1970s and 80s and then abandoned - its success now indicates that investigation of a family of known pharmacologically active compounds with newly available technologies may be a good low-cost approach to take.
However, these technologies must also be used to study fundamental aspects of parasite biology to identify new therapeutic targets, which is the approach my lab has taken.
The focus of my PhD project is the trypanosome transport system, which is one of the main factors that enable it to survive in the host. This system maintains the surface of the trypanosome, which is entirely covered by a dense coat of a molecule called "variant surface glycoprotein" - VSG - which forms an impenetrable barrier against the host immune system. Additionally, the swift and streamlined nature of the system enables trypanosomes to internalise and neutralise any antibodies that our immune system produces against this VSG. It also enables them to replace the existing coat with newly produced modified VSGs which our immune system can no longer recognise and act against.
Recent advances in genome sequencing have given us complete DNA sequences of several disease-causing parasites. I am using these resources to study the evolutionary history of the proteins that make up the transport system in trypanosomes. I have also started to use proteomics to find novel interacting partners of key players in the transport system in order to build up our understanding of the structure of the system in trypanosomes compared to, say, our own cells.
Evolutionary analysis combined with proteomics enables us to pick up proteins that are present in trypanosomes and are essential for their survival, but are not present in mammals. They can therefore be a powerful way of uncovering and elucidating potential parasite-specific drug targets.
Of course, this is only the first step - and things get more expensive as a drug candidate goes through the clinical trials system. In recognition of the acute suffering these diseases cause, increased investment from foundations, governments and pharmaceutical companies are an important part of the solution. But in the long term, it is also important to have R&D and intellectual property systems that don't depend on donations to function.Suggest a correction