Project background
Clean water: a privilege and luxury many take for granted. Swimming: a leisurely activity we enjoy, without fearing we will end up with a chronic parasitic disease. Although these things hold true for most of us, it is not the case for many populations around the world. According to the CDC, 2 billion people lack access to safe drinking water, while 3.6 billion people don’t have access to proper sanitation in their homes—and the effects are concerning. Not having proper water, sanitation, and hygiene (WASH) can exacerbate the risk of deadly tropical diseases, affecting those living in rural, low-income areas. . Despite the high rates of infection and morbidity, most of these diseases have little to no recognition in the academic world.
Schistosomiasis is one of the neglected tropical diseases (NTDs) that plagues millions of people globally. The disease is prompted by direct contact with infested water holding parasitic worms called schistosomes. Schistosomes enter the bloodstream through the skin and lay eggs that can become trapped in body tissues, causing severe immune reactions and damage to internal organs. Although schistosomiasis is currently being treated by a prescription called praziquantel, reinfection rates are high and resistance to medication is possible. Therefore, it is worthwhile to research new and improved interventions that may reduce morbidity.
Research question
Working alongside Dr. Patrick Skelly in the Molecular Helminthology Lab at the Cummings Veterinary School, I will be researching nanobodies that target schistosome surface enzymes as a novel intervention to control schistosomiasis. At the moment, the lab has already identified three enzymes (SmT-AChE, SmNPP5 and SmCA) that are expressed on the skin of the schistosomes. Each of these three enzymes is essential for robust infection of the vertebrate host by the parasites, making them rational targets for therapeutic intervention. The antibodies that bind to schistosome enzymes originate from alpacas. This summer, I will work to monitor the ability of nanobodies to bind to their targets, both in a test tube and on the parasites. Ultimately, I hope to answer the question “how can we identify useful, schistosome-binding nanobodies that may, in the long-term, be useful therapeutically to treat schistosomiasis?”
Methodology
We will be monitoring the ability of nanobodies to bind to their targets using standard ELISAs (enzyme-linked immunosorbent assays), and then by immunofluorescence microscopy on parasites. Next, we will be testing the ability of the nanobodies to block enzyme function. This will be done using protein assays to measure the function and effectiveness of these nanobodies. While monitoring the ability of nanobodies to bind to their targets in parasites, microscopy will be used to find the location of where the nanobodies bind on the worms.
Objectives
In the long-term, I hope this research will help with studies in which nanobodies could be used therapeutically to treat infection in humans and animals. Through working on this project, I hope to gain a more comprehensive understanding of the biology of schistosomiasis. In addition to understanding these research mechanisms, I want to hone a deeper understanding of how neglected tropical diseases can be prevented and treated beyond solely therapeutic intervention. I hope to accomplish this goal through leveraging Laidlaw’s leadership programming and connecting with fellow scholars who have researched other NTDs and WASH interventions.