Dr. Rupert Kaul
Dr. Rupert Kaul. Image credit: Mayra Cruz Tleugabulova.

The global challenge presented by the AIDS epidemic, by necessity, requires modern-day HIV and AIDS research to be ever more interdisciplinary and collaborative. This mentality is thoroughly embraced by Dr. Rupert Kaul, who leads an HIV research group in the Department of Immunology that combines virology, immunology and epidemiology in an effort to better understand the transmission patterns and pathogenesis of this lethal virus. In addition to running a lab in Toronto, Rupert has been working in the very HIV/AIDS-relevant locales of Kenya and Uganda for many years. In this issue of IMMpress, we take a look at how these international projects came to fruition and the nature of his HIV research in East Africa.

THE ADVENTURE THAT SPARKED A CAREER
After finishing his medical specialty training in Infectious Diseases at the University of Toronto in 1995, Rupert was eager for a fresh challenge. Shortly after, he accepted an invitation from Dr. Frank Plummer, a titan of HIV research hailing from the University of Manitoba, to join him for a nine-month research fellowship in Nairobi, Kenya. “At the time, I was really looking for a change of scenery rather than a career,” Rupert reminisces.

In what turned out to be a defining moment in his training, Rupert spent several months studying the epidemiology of HIV transmission within cohorts of Kenyan sex workers prior to enrolling in an immunology PhD program under co-supervision by Dr. Frank Plummer and Dr. Sarah Rowland-Jones at the Institute for Molecular Medicine (Oxford, UK), which he completed in 2002. After returning to Toronto to set up his own lab, Rupert not only maintained the collaborations he established in Kenya, but has continuously expanded his international focus over time, initiating additional collaborative projects within the Rakai district of south-west Uganda in 2009.

PRIME LOCALES FOR CUTTING-EDGE HIV RESEARCH
Given that the majority of new HIV cases occur through sexual transmission, Rupert’s primary research interests involve understanding the characteristics of the immune response in the genital mucosa (both female and male) in HIV-infected and at-risk people. His research projects in Kenya and Uganda primarily centre on the study of the various immune factors and cell populations within the cervix and foreskin, and how these are related to the risk of HIV acquisition. With HIV prevalence simmering just below 10% within the densely populated urban areas of Nairobi and Kampala, the capitals of Kenya and Uganda respectively, these are ideal locations to study HIV susceptibility in the general population. Rupert hopes that the insights gained from his research may lead to the implementation of improved local prevention programs.

However, in order to perform immunology research in the context of large-scale clinical studies, a certain level of research infrastructure is required. Rupert works within the context of a formal memorandum of understanding (MOU) that he established with the Department of Medical Microbiology at the University of Nairobi. He and his students make use of a state-of-the-art research facility belonging to the University’s Department of Medical Microbiology, built with funding from the Canadian Foundation for Innovation (CFI) under the guidance of Manitoba collaborator Dr. Keith Fowke. This MOU facilitates bilateral collaboration between Canadian and Kenyan investigators as well as the training of students from both countries. The facility itself is equipped with all the tools an immunologist would need to perform innovative HIV research: two BSL3 labs, one with BSL4 capacity, bench space equipped with multi-parameter flow cytometers, sequencers, fluorescence microscopes and more.

Similar technology can also be found within the Rakai district of Uganda, where collaborations with Johns Hopkins University, the UK’s Medical Research Council, the Uganda Virus Research Institute and Makerere University have established a fully-fledged international research collective. Both the Nairobi and Rakai sites have residences near campus or off-site apartments set up to accommodate students and fellows arriving from abroad. Since the inception of his lab in Toronto, Rupert has frequently traveled to and from these sites and furthermore, has facilitated the exchange of many of his own students and postdocs who make the trip to Kenya or Uganda to complete immunological studies of a greater scope and relevance than what could be achieved in Toronto.

A UNIQUE RESEARCH VENTURE FOR UNIQUE PERSONALITIES
Even though the programs are in place to send students from Toronto to Nairobi or Rakai, the decision to commit to these projects is understandably difficult. For one, the projects range from a few weeks to several months in length. Even though accommodation and transport costs are taken care of with a combination of CIHR studentships and project-specific grants, the remote location and different way of life can still represent a substantial culture shock. Students who participate in one of these projects leave their life in Canada behind for a significant period of time; not everyone can make this choice depending on their responsibilities or family situation. In addition, Rupert mentions that only certain types of personalities can thrive in the very different research environment that will greet them in Africa.

“Usually I’ll send students for a small pilot project that lasts several weeks, not only for them to assess their new surroundings, but for the local staff to assess them,” explains Rupert. “If everyone gets along then it opens the doors down the road for a more in-depth study that could take a few months, or even years, to complete.”

Overlooking one of many villages on the outskirts of Nairobi, Kenya.
Overlooking one of many villages on the outskirts of Nairobi, Kenya.

Crucially, keeping these highly collaborative studies running smoothly requires a healthy working partnership between the visiting students and the local staff.  Students who are personable and can adapt quickly to working with a variety of collaborators – clinicians, nurses, health workers, and technicians – will make the most of their time abroad. When Rupert discusses potential projects with a prospective graduate student, he always mentions which ones involve research time overseas. Quite often, the prospect of carrying out an HIV research project in Kenya or Uganda is a major reason why many students are so attracted to Rupert’s lab in the first place.

The Department of Medical Microbiology research building on campus at the University of Nairobi, Kenya.
The Department of Medical Microbiology research building on campus at the University of Nairobi, Kenya.

GREAT RISK AND REWARD COMBINE FOR A CHALLENGING EXPERIENCE
On paper, the opportunity to lead a comprehensive research project with diverse and substantial participant cohorts in Kenya or Uganda is one that would excite any ambitious student. However, even though the equipment and techniques used in the Nairobi or Uganda research facilities are comparable to those in Toronto, the research environment is a different animal entirely. Vineet Joag, a PhD student from Rupert’s lab who worked in the University of Nairobi research facility on two separate occasions, remembers that the working culture he initially experienced in Kenya certainly took time to get used to. He mentions, “While it is a challenge to begin work in any new environment, you have to be especially conscious that you are being welcomed into a different culture. One should try to be especially adaptable to existing working practises and norms, and while it took me a couple of weeks to get accustomed, my co-workers were very friendly and helped me fit right in.” Moreover, the research questions that can be addressed are unique, and a student who is willing to take on multiple responsibilities and apply a very hands-on approach to their research can thrive.

Vineet not only completed a project in Nairobi but enjoyed his time working there as well. He mentions certain traits that one should possess or at the very least, adopt, in order to succeed. Firstly, you have to be meticulous and organized, and have the logistics of the project planned well in advance of your arrival. “Most of the reagents and disposables – antibodies, culture plates, media/buffer bottles and even pipette tips – are your responsibility since it can be expensive and time consuming to purchase supplies on demand,” recalls Vineet. Patience and adaptability are also virtues that can help you integrate into a very different working environment. “Not everything goes according to plan,” a tried and tested graduate student motto, is doubly true considering the unpredictable circumstances when working on one of these projects abroad.

CAPACITY BUILDING – A SURMOUNTABLE CHALLENGE?
Both Rupert and Vineet agree that there are important differences between the research opportunities and infrastructure available in East Africa when compared to Canada. A lack of stable long-term funding for Kenyan collaborators can lead to a higher turnover of local technicians, which makes knowledge transfer of research practices challenging. The critical interdependency between multiple staff and research associates means that managing these highly-collaborative studies is a very different beast compared to running a more focused research team working within the confines of a single lab. Certainly, the ability to transfer technical expertise in a sustainable fashion is a considerable obstacle that Rupert acknowledges has yet to be solved.

PhD students Jessica Prodger and Ronald Galiwango at work in the International AIDS Vaccine Initiative (IAVI) laboratory at the Uganda Virus Research Institute (UVRI) in Entebbe, Uganda.
PhD students Jessica Prodger and Ronald Galiwango at work in the International AIDS Vaccine Initiative (IAVI) laboratory at the Uganda Virus Research Institute (UVRI) in Entebbe, Uganda.

“The number one challenge for HIV research in East Africa is to build, and particularly, to maintain capacity,” Rupert mentions. What he refers to is the expansion of programs that can help establish a more organized culture of research within sites like Nairobi or Rakai. Grants that not only fund research studies but also focus on building long-term systems for training, mentorship, and education of local researchers would be steps in the right direction. Canadian agencies such as the International Development Research Centre (IDRC) and CIHR’s Social Research Centre (SRC) have provided short-term opportunities for Kenyan students and fellows, and the hope is that the University of Toronto wmay follow suit and “buy in” to provide further support. In particular, this would provide, among other things, prospects for Kenyan students to come to the University of Toronto for training and research opportunities. “Ultimately, the goal of our collaborative international research is to not only succeed with our own projects, but to help train the next generation of East African researchers, and to build a sustainable and independent research culture,” Rupert adds. The benefits would be two-fold: local research teams could lead and complete independent studies and when international collaborations do occur, these studies could be locally driven and be carried out more efficiently and with greater ambition.

The Rakai Health Sciences Program in Uganda is one of the oldest and largest collaborative HIV/AIDS research programs in Africa.
The Rakai Health Sciences Program in Uganda is one of the oldest and largest collaborative HIV/AIDS research programs in Africa.

Rupert has no plans to slow down the programs that he has established in East Africa. A significant number of the studies that his group has published involve research performed by his trainees staying in Kenya and Uganda, and by his local colleagues from those countries. In addition, other groups in our Department – the Ostrowski, Macdonald, and Gommerman labs – have performed, or are planning, similar collaborations in Nairobi and Rakai. These collaborations, much like the projects that Rupert has been a part of for almost two decades, will help us learn more and more about how the immune system interacts with HIV, especially in areas where these insights are of paramount importance.

Acknowledgements
Special thanks to Dr. Rupert Kaul, Sergey Yegorov, and Vineet Joag, whose interviews, discussions, and edits contributed enormously to this article.

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Michael Le

Managing Editor
Michael is a 4th year PhD student in the Department of Immunology at the University of Toronto studying how B cells diversify their antibodies to fight infections. He enjoys staying active, playing board games, and supporting his beloved Arsenal FC.

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