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Exploring STEVOR Proteins: Hristina's PhD Journey in Malaria Research

In this blog, Hristina shares her journey through a PhD focused on understudied malaria proteins, overcoming challenges, and her discoveries that could impact future research in Plasmodium falciparum.
malaria centre member Hristina Vasileva

Can you briefly describe your research focus and the key findings of your PhD?

My PhD research focuses on investigating understudied protein families in Plasmodium falciparum that are associated with disease pathology. The primary objective is to examine the antigenicity and antigenic variation of these proteins by analysing global protein sequence data. Specifically, I studied the STEVOR protein family and created a library of recombinant antigens in the lab. These antigens were tested on serum samples from individuals of all ages across Sub-Saharan Africa, with varying levels of malaria endemicity.

A key finding of my project is the first demonstration of the global variation of the STEVOR family using an in-silico model I developed, which can be applied to sequence data from any organism to assess protein variation and similarities. Additionally, I discovered that antibody responses to STEVOR proteins are generated rapidly after initial infection, and the strength of the response is not determined by the level of exposure—unlike what is typically observed in similar protein families. This suggests that the parasite’s strategy of expressing such a high variety of STEVOR proteins may align with the 'smokescreen' theory, where the parasite overwhelms the immune system with a broad array of antigens, concealing key members that are critical to disease pathology.

What motivated you to pursue a PhD in your field?

I completed my MSc in Medical Microbiology at LSHTM from 2016 to 2017, where I encountered a remarkable group of researchers, from Scientific Officers to Professors. This experience shifted my career focus from becoming a clinical microbiologist to pursuing research in tropical medicine. After my MSc, I worked as a Scientific Officer on various projects and diseases under the guidance of my future supervisor, Anna Last. During this time, I also joined the malaria immunology team, where I met my second supervisor, Kevin Tetteh.

Everything fell into place when Anna asked me to lead the laboratory work for a new clinical trial based in Guinea-Bissau at the MRC Unit in The Gambia, with the opportunity to pursue a PhD. Kevin and I then developed the idea for my PhD project, and the journey began. Four years and five months later, including one pandemic, working in three countries, completing a thesis, attending several conferences, and receiving a Director's Award, I successfully passed my Viva. I am now a Research Fellow under Alfred Ngwa at the MRC Unit in The Gambia, continuing my work in malaria research by building on my immunology expertise and exploring new techniques in malaria genomics, both in the wet lab and in data analysis.

What were some of the biggest challenges you faced during your PhD journey, and how did you overcome them?

One of the biggest challenges I faced was balancing a full-time job working on the MATAMAL trial while simultaneously pursuing my PhD, all within the constraints of a 24-hour day. Effective time management and prioritizing tasks were crucial to staying on top of both responsibilities. Another major challenge was the COVID-19 pandemic, which, like for many others, slowed down my work and introduced difficulties in conducting my research. Fortunately, I was granted an additional year of funding to compensate for the delays caused by the pandemic, and I am grateful to my supervisors and funders for their support and understanding.

Can you share a particularly memorable moment or breakthrough during your research?

One of my most memorable experiences was during my fieldwork on the Bijagos Islands in Guinea-Bissau, a four-hour ferry ride from Bissau. I spent three months there collecting dry blood spots while living in a tent in remote areas without cars, money, electricity, or running water. I learned to speak Portuguese Creole and became part of the local community. This experience taught me invaluable lessons about humanity, appreciating the small things, and being grateful for what we often take for granted every day.

How did you balance your PhD work with other aspects of your life?

I often say that a PhD and research aren't just jobs—they’re a lifestyle. To reach your goals and ensure the quality of your results and interpretations, personal sacrifices are often necessary. However, it’s all worthwhile when you start to reap the rewards of the hard work you’ve put in along the way. Despite the demands of my PhD, I’ve always made time for something I love: playing sports. I made a point to continue this during my PhD, which involved regular training sessions, trials, and participating in both national and international competitions. This passion has been beneficial for my PhD journey, as it helped me manage stress, reduce mental fatigue, and stay fit and healthy throughout.

My advice to other busy researchers, regardless of their career stage, is to find time to unwind by doing something they love. In my opinion, regular physical activity is one of the best ways to do that. As for other aspects of my personal life, it has been challenging to find time for family and friends, but I’m fortunate to have a supportive circle that understand the demands of my work. Sometimes, we all have to make sacrifices in one area to achieve success in another.

Who were the most influential mentors or supporters during your PhD journey?

Throughout my PhD journey, I have often praised my supervisors, Anna Last and Kevin Tetteh, for their guidance. However, it’s equally important to acknowledge the people behind the scenes who consistently supported me and provided additional mentorship. There are many—from fellow PhD students to my family—but I would especially like to mention David Mabey, Martin Holland, and Martin Goodier. Their scientific expertise and personal support were invaluable to me during this time.

What advice would you give to someone considering pursuing a PhD?

It's crucial to be passionate about your research topic. A PhD requires continuous perseverance, and that passion will help you push through the challenges. I would also recommend attending as many conferences and presentation opportunities as possible, as these can spark valuable discussions and help you think more critically about your results.

What are your plans and aspirations now that you have completed your PhD?

I am currently a Research Fellow and actively seeking grant opportunities. My goal is to advance my research career by becoming the Principal Investigator (PI) of my own project.

How do you think your research can impact the broader community or your field of study?

From the start, my project has been highly ambitious. Given the limited literature on STEVOR proteins, I believe my research significantly contributes to closing the knowledge gap in the Plasmodium falciparum proteome. Additionally, my computational model, which investigates and visualises relationships between sequences, can be applied to any organism, making it valuable to the wider scientific community.

What’s next?

A colleague, who is also a good friend, and I have an exciting, innovative research idea that we’re currently refining and aiming to present to the right funder. I won’t share too much for now—stay tuned!

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