Having come from an international background between India, Germany and the France, Venkat Mudiyam, a doctoral student at the Pasteur Institute of Lille, specializes in the study of apicomplexan parasitess, responsible for major diseases such as malaria or ToxoplasmosisHis research focuses on the fundamental mechanisms of their biology, from their multiplication to their ability to persist in the organismIn this interview, he reflects on his career path, his motivations, and the challenges of his work, which aims to better understand these parasites in order to pave the way for... new therapeutic strategies.
Can you tell us about your background and what led you, from India to Germany and then to France, to specialize in the study of apicomplexan parasites?
Venkat Mudiyam (VM) I obtained a Bachelor of Engineering in Biotechnology in India. I realized that biological sciences were interesting, but since it was an engineering degree, I always felt that my foundation in fundamental life sciences wasn't as strong as I would have liked. To gain this knowledge and experience, I joined in 2019 the laboratory of Shruthi Vembar as a research assistant, where I worked on the human malaria parasite Plasmodium falciparum.
My initial plan was to go abroad for a master's degree after a year, but the COVID-19 pandemic hit and changed everything. So I stayed in the lab for another year, which turned out to be a very enriching experience. After that, I went to Germany to pursue a master's degree in molecular cell biology at the University of Bonn.
During this master's program, I had the opportunity to work on a variety of topics, ranging from stability from genome to immunology, including disease modeling using induced pluripotent stem cells (iPSCs)But through it all, I realized that I always came back to the apicomplexan parasitesThis interest has never really left me.
Around that time, I contacted my friend Maanasa, who had done her PhD at the Pasteur Institute in Lille with Mathieu Gissot, who is now my supervisor. Thanks to her, I was able to learn more about his work. I read some of his articles and felt that his research perfectly matched what I wanted to do. apply molecular biology approaches and cellular to understand the biology of parasites, with the ultimate goal to identify new therapeutic targetsSo I wrote to him to inquire about PhD opportunities.
He replied quite quickly, and we had a very interesting discussion about possible projects and the doctoral program at the Pasteur Institute of Lille. We eventually drafted a proposal together to study a family of transcription factors called ApiAP2. Fortunately, it was successful, and I got the position, and here I am at the Pasteur Institute of Lille today!
What particularly attracted you to parasites like Plasmodium ou Toxoplasma gondiiresponsible for major diseases such as malaria or toxoplasmosis?
VM: My interest in apicomplexan parasites (Plasmodium, Toxoplasm et Cryptosporidium) is based on both scientific and personal reasons.
From a scientific perspective, I am fascinated by the biology of these parasites, their ability to invade human cells, establish an infection, and evade the immune response when necessary. I am also intrigued by their ability to persist in the host for many years. in the form of dormant cystsand then to reactivate later to cause illness without further infection.
Their apical apparatus, which is the origin of the term "apicomplexes", is particularly fascinating to me because it allows them to inject a set of proteins and establish a niche within host cells; Some of these proteins also modify the host's cellular processesThese parasites are responsible for some of the deadliest diseases, and there are still no fully effective vaccines against many of them.
On a personal level, coming from a country like India, where these parasites are very widespread, naturally drew my attention to this subject.
The blue signal corresponds to DAPI, used for DNA labeling, while the red signal highlights alpha-tubulin, a major component of the cytoskeleton and mitotic spindle.
Credits: Venkat Mudiyam, API-B team
Your team is interested in how these parasites multiply and persist in the body. Specifically, why are these two abilities so important for understanding the disease?
VM: Proliferation refers to the rate at which the parasite multiplies in the organism, and it is very important for a parasite like Toxoplasma gondiiThe faster it multiplies, the more cells it infects and damages, leading to more pronounced symptoms and a more severe disease.
Persistence, on the other hand, refers to the parasite's ability to remain in the body for a long time in the form of cysts, often evading the immune system. This means that the infection can not not be completely eliminated and can reactivate later, especially if the immune system weakens.
To fully understand the disease, it is necessary to consider both the speed of parasite propagation and ability to survive over timeTogether, these two properties explain why infections can be both severe in the short term and difficult to eliminate in the long term.
Your work explores very fine-grained regulatory mechanisms, including cell division and the control of gene expression in Toxoplasma gondiiWhy is it essential to understand these very early and very “microscopic” stages of the parasite's life cycle?
VM: These parasites are very small, about 3 micrometers (0,0003 cm). Even though these processes occur on a microscopic scale, they control everything the parasite does. Studying them is obviously not easy due to the extremely small size of these structures. To achieve this, we also use a very powerful approach called ultrastructural expansion microscopy, initially developed by the laboratory by Edward Boyden au MIT and adapted to apicomplex parasites by several teams.
Studying cell division helps us understand how quickly the parasite multiplies, while gene expression determines which genes are activated ou repressed at different stagesThis is particularly important because the parasite must finely adjust its different forms according to its environment within the host.
If these early regulatory mechanisms malfunction, the parasite cannot grow, adapt, or survive. By understanding them, we shed light on the biological processes that govern its life cycle. These stages are often very precise and critical, making them good potential targets for new treatmentsIf we can disrupt these early processes, we could prevent the infection from spreading or becoming chronic.
How can this fundamental research ultimately pave the way for new therapeutic strategies against these parasitic infections?
VM: By understanding the basic biology of the parasite, we can identify the vulnerabilities which underpin its survival, and these can constitute excellent therapeutic targets.
For example, our team is working on a family of transcription factors specific to apicomplexan parasites, which are absent in their hosts. Most of the transcription factors in this family have been shown, or are predicted, to be essential for the parasite's survival and persistence. If we can inhibit these transcription factors, we could disrupt their cell cycle and growth.
You are also a member of the Young People's Association of the Pasteur Institute of Lille (YPL). Can you tell us more about this association and what your involvement brings you, both personally and professionally?
VM: YPL (Association of Young People of the Pasteur Institute of Lille) is an association that brings together doctoral students and researchers from the Pasteur Institute of Lille. Its main purpose is to create a sense of community among young scientists, to organize scientific and social events, and to promote exchanges between the different research groups and disciplines within the institute.
For me, being part of the YPL has been beneficial both personally and professionally. On a personal level, it has helped me to better integrate into the institute, to meet researchers outside my laboratory and to feel more connected to the scientific community as a whole. Arriving in a new country without speaking French, this sense of community was particularly important. We also seek to to offer the same welcome to newcomers.
On a professional level, this has allowed me to better understand the organization of scientific activities and events, as well as how to to promote communication between laboratories and disciplinesThis also helped me improve my ability to interact with researchers from diverse backgrounds and to discuss science beyond my own project. Overall, it was an excellent complement to my doctoral trainingand I look forward to contributing to upcoming projects.
