There are many different routes into a career in immunology, and a vast range of possible career paths within the field. Immunologists often require a wide range of skills and knowledge to effectively adapt to the ever-changing landscape. Our Career Enhancing Grants provide flexible financial support to help immunologists grasp opportunities and tackle challenges along the way. Here, Dr Priscilla Tng describes how the grant helped shape her own research trajectory.
An unconventional route
My path into veterinary immunology is perhaps more unconventional than most. I began my career in the field of combat trauma care research in Singapore, before coming to the UK to undertake research on developing gene drive systems in mosquitoes. During my PhD I explored methods to engineer mosquito strains to be resistant to infection by the alphavirus chikungunya, and this sparked a broader interest in host–pathogen interactions. I then sought to combine my previous research experience with large animals, synthetic biology and host immunity by joining the African Swine Fever Vaccinology group at the Pirbright Institute. My post-doctoral project focused on developing a subunit vaccine for African swine fever virus, through the identification of immunogenic antigens.
African swine fever
African swine fever virus is currently circulating in Africa, Asia, Europe and the Caribbean, and is a significant threat to the global pig population and the associated industries. The virus induces a haemorrhagic disease in pigs and wild boar that is almost always fatal. There are no treatments available, and no vaccines licensed for use in major pork-producing regions such as China, America and Europe. The main control measures involve culling and movement control of animals, which result in high economic losses and impact global food security. Furthermore, vaccine development is hampered by the complexity of African swine fever virus (its genome is six times larger than that of SARS-CoV-2) as well as a lack of African swine fever immunology research. Understanding the impact of the virus on a host's immune responses is crucial for developing effective interventions.
Advantageous organ cultures
Most recently, I have been exploring the fascinating area of ex vivo organ cultures, which enable us to study the heterogenous mix of cells outside the living organism. These organ-derived cultures allow us to study the effects of multiple virus strains separately in a single host, while preserving crucial cell-to-cell interactions. They are particularly useful for conducting detailed time-course studies, and for capturing time-sensitive processes such as host responses to viral entry and early viral replication in infection-relevant tissues – tasks that are challenging to achieve with in vivo studies. Organ cultures are by no means a complete substitute for in vivo studies, but they are a closer approximation than currently used in vitro methods. Although significant progress has been made in human and mouse immunology research using organ cultures, veterinary immunology is still in its nascent stages in this area. My focus is on the lymphoid organs, and in particular the complex dynamics of immune cell populations induced by African swine fever virus in these organs.
Embarking on this journey, I was motivated by the need to develop new approaches that could shed light on cell-to-cell interactions at the tissue and organ levels, with the ultimate goal of minimising the suffering of animals affected by this lethal virus. My observations led me to an important realisation: most studies focused on virus–host interactions in primary macrophage cultures, which are the primary target cells for the virus. However, at the tissue and organ level, African swine fever virus replicates mainly in lymphoid tissues such as the spleen.
A BSI boost
Ethical concerns surrounding animal use make it challenging to explore interactions at the early stages of infection in the spleen. This is where the BSI Career Enhancing Grant played a key role in reshaping my research trajectory. With the funding, I set out to establish if it was possible to derive viable ex vivo cell cultures from the pig spleen. Using waste tissues from pigs, I established both fresh and frozen-thawed cultures and assessed the presence and viability of organ-derived cell populations over time. I discovered that certain cell populations were more sensitive to culturing and freezing processes and determined that fresh cultures were more suitable for my research. These cultures allowed me to study the effects of African swine fever virus infection on immune cell populations for up to five days.
The grant not only facilitated the development of these cultures but also allowed me to enhance the existing immune cell phenotyping panels for these experiments. I was able to add new surface markers and intracellular cytokine markers that expanded the breadth and depth of my analyses. These helped to identify diverse infection profiles of different African swine fever virus strains and the differential infection rates between the strains in these cell populations. Spectral flow cytometry emerged as a valuable tool in this process, enabling a more nuanced analysis of the immune cell populations. I was able to develop my flow cytometry analysis skills and found myself delving into more sophisticated methods of analysis.
The pilot data generated through these improved methods proved to be invaluable, forming a foundation for advancing the understanding of African swine fever virus-induced lymphocyte population dynamics. The differences in infection profiles and cell preferences highlighted gaps that warranted further investigation to determine if specific immune cell populations afford resilience to African swine fever virus. Identifying and studying such cell populations may provide valuable insights for enhancing protective immune responses.
Further funding
The BSI Career Enhancing Grant enabled me to demonstrate the feasibility of using spleen-derived organ cultures to investigate the effects of African swine fever virus, and this early work became crucial in securing additional funding. Using the insights gained, I applied for the Biotechnology and Biological Sciences Research Council’s Discovery Fellowship and was successful in my application. This further funding confirms the importance of the initial findings, not only as a catalyst for further exploration, but as a testament to the impact of the BSI Career Enhancing Grant on advancing my work. The skills and knowledge I have acquired and refined during this period are building blocks that will be instrumental in shaping my career in veterinary infectious diseases. The grant not only fuelled my scientific inquiry but also enabled me to contribute to the refinement of techniques and methods in the field of veterinary immunology. These improvements are valuable for other researchers in porcine immunology and can be further developed and adapted for in vivo studies within the broader research field.
This preliminary work contributes to my research goals of understanding immune pathways and mechanisms that protect pigs from African swine fever virus. My aim is to identify targets that can help in the design of effective vaccines and to guide genetic selection for more resilient pigs. I am particularly intrigued by the variations in host responses to different strains of the virus, and this study lays the groundwork for further exploration in this area.
Advice for future applicants
It is with much gratitude that I acknowledge the British Society for Immunology's foresight in supporting early career researchers. This grant has played a vital role in advancing our understanding of immune cell population dynamics at the tissue level in African swine fever virus. It has helped me to build a path towards more refined experimental methods and, ultimately, effective interventions for African swine fever virus. As such, it has contributed to a future where compassion and knowledge converge for the advancement of veterinary science.
For anyone who is interested in applying for this grant, I recommend seeking feedback on your ideas from peers or mentors. Additionally, take time to consider how your proposed project addresses gaps or challenges within your field and how it contributes to solving real-world problems. This will not only strengthen your application but also increase the potential impact of your research. Finally, take the chance and apply – you never know what doors it might open.
Dr Priscilla Tng, The Pirbright Institute