Interview: Private Lecturer Minka Breloer
Zebu cattle in Ngaundere, Cameroon
© Manchang Tanyi Kingsley
Private lecturer Dr. Minka Breloer directs the "Helminth Immunology" working group at the Bernhard Nocht Institute for Tropical Medicine (BNI). Together with PD Dr. Norbert Brattig from the Department of Molecular Medicine, she represents the BNI as a partner in the German-African collaborative project "Analysis of Host-Parasite Cross-Talk Based on the Bovine Model for Human Onchocerciasis, Onchocerca Ochengi", which the DFG has funded since 2009. Working together here are four German partner institutes at the universities of Münster, Tübingen as well as DESY and the BNI with Cameroonian partners from the university in Ngaoundere and the "Institute Agricultural Research for Development" (IRAD) in Wakwa.
What is the thematic background of the project?
We are studying parasitic worms. They differ from other pathogens in their size – compared to viruses or bacteria, they are huge. Worms enter their hosts (i.e., humans) and parasitise there in spite of their size in some cases for years and decades. They accomplish this by actively dampening our immune response. Our immune system has "built-in" negative feedback controls to quickly end immune responses and to prevent immune reactions from overshooting. The worms can use these feedback controls to overactivate immune cells with damping function. In this way, they succeed in evading our immune response. We ask ourselves how exactly the worm interacts with the immune system of the host and, conversely, how the host affects the development of the worm. We are studying this communication between parasite and host in the model of the Onchocerca ochengi worm, which infects zebu cattle. Because O. ochengi is closely related to the human-pathogenic Onchocerca volvulus, the pathogen responsible for river blindness, the results from this system can, in my option, be better applied to humans than findings that were gained in the mouse models from thread worm infections, which I worked with previously.
How are you approaching the problem?
We suspect that the worms release protein molecules which ensure that the immune system is switched off. In Cameroon, our partners have acquired a herd of cattle with more than 20 calves that graze in a pasture along a river near Ngaoundere where O. ochengi is endemic and is transmitted by mosquitoes of genus Simulium. For me, as someone who has previously worked only on the mouse model, this is very fascinating. First, our partners on-site prepared worms from the infected cattle and harvested protein molecules released by the worms (excretory/secretory proteins or ESPs). In Germany, our experts for biochemistry used the latest methods to separate this protein mixture into the individual components and determine the nature of the proteins with mass spectrometry. Our molecular biological experts could then recombinantly, i.e., in a test tube, produce a protein that was identified in this way. My working group then receives these proteins for immunological characterisation. On the one hand, we use various models with immune cells from the mouse to study whether and how these proteins can dampen immune responses. On the other hand, we return to the infected cattle in Cameroon with exactly these proteins and study whether they could as well be the target of a protective immune response. In addition, blood samples were taken from the cattle before the infection and at various times after the infection. Our partners in Cameroon are studying on-site which proteins are detected by antibodies or by the immune cells of the cattle.
What effect does the project have on-site in Cameroon?
The infection of cattle with O. ochengi is a significant problem for cattle farming on-site, and the related human pathogen o. volvulus infects an estimated 5 million people of whom approximately 30,000 are blinded as a result of the infection. In our project, we are gathering important knowledge on the course of worm infections. Nevertheless, with such questions I always like to point out the DFG does not promote African health policy, even in the German-African projects on infectology, but rather primarily promotes projects that are scientifically outstanding. As we are studying the communication between parasitic worm and host, we are first and foremost performing basic research. Such projects do not necessarily have an immediate impact on the health situation at the local site. In the long term, a better understanding of this host/parasite communication will, however, serve as the basis for the development of better treatments and vaccines. In my opinion, only basic research with its "long-term approach" is truly capable of preparing for unexpected problems and future developments, such as the occurrence of new infections or complications.
© Minka Breloer
What might an added value look like?
With our project, we can, of course, identify good vaccine candidates and show paths to medications with fewer side effects. Many people live with a worm infection without dramatic symptoms, but do have a weakened immune system due to the immunosuppressive activity of the worm. As a result, vaccinations may not function in these people, as we recently demonstrated in a mouse model (Hartmann et al., 2011 Journal of Immunology). If we can better understand exactly how the worm switches off the immune system, we can develop vaccines that work independent of the infection status of the patient.
How did you come to be involved with the project?
Previously, I performed purely immunological basic research, but had always been interested in the regulation of our immune responses. Just over three years ago, I took over leadership of a working group that was to concentrate on pathogenic, i.e., disease-transmitting, worms. I was then contacted by the leading applicant, Professor Eva Liebau from the University of Münster, who I already knew from the Bernhard Nocht Institute for Tropical Medicine (BNI) – as I had already started to examine the immunological feedback control circuits, using the example of worm infections in mice. So, I was brought on board to provide immunological expertise. Maybe I am good example of how a researcher's horizon can be expanded within the scope of a cooperation project, as, without the project, I certainly never would have had access to worm-infected cattle or ESP from O. ochengi.
How do you cooperate with your partners?
In the description of our strategy, you have already seen that all partners must combine their respective expertise (veterinary medicine, parasitology, biochemistry, molecular biology and immunology) to be able to jointly study the question of host/parasite interaction. Thanks to the funding, I personally had the opportunity to hire a doctoral researcher from Cameroon, Manchang Tanyi Kingsley, for three years and to further train him in my working group. We have, mainly at the University of Münster, many master's students from molecular biology who travel to Cameroon for several months within the scope of the project – as well as many Cameroonian students who come here. In addition to the scientific education, I believe that the human contacts thereby established are important. Particularly through the personal contact with the young researchers at the start of their careers, a network is renewed that is very sustainable and which will also lead to further contacts beyond this project. A German researcher who, for example, personally knows researchers in Cameroon from when he worked on his master's thesis and, ideally, had good experiences during the collaboration, will much more easily be able to establish an efficient collaboration if he later becomes the leader of a working group or a professor. In addition to the scientific findings, I see this as one of the most important successes of this project: the personal contacts that are established between Germany and Cameroon in this cooperation.
How do you experience science in Cameroon?
For me, the collaboration with my Cameroonian doctoral researcher is the first long-term contact and this exchange is very exciting for me. It is clear that science is organised and financed much differently in Cameroon than with us. In Germany, good researchers should change their research institute every five years and have serious problems finding an indefinite position, something which may, for example, be a prerequisite for family planning. As I understand it, if a person in Cameroon lands a position, it is often immediately for life. Instead, the researchers there often have enormous problems to raise the funding necessary for performing research. It happens that they are paid their full salary, but sit practically idle in their laboratories because they aren't able to purchase test tubes. In this regard as well, the cooperation project is, of course, a blessing. In early 2012, I will travel for the first time to our cooperation partners in Cameroon for an expected period of two weeks, during which time I will be able to personally form a more comprehensive picture.
What ideas do you have for the future?
The topic of immunoregulation runs through my research and I find it very exciting to now work in cooperation with an African partner. My vision would be to establish more complex immunological methods, such as the flow cytometry that we use in Germany, in Cameroon step-by-step. The combination of the "Cameroonian possibilities", the studying of natural worm infections in more than 20 cattle with the establishment of modern immunological techniques on-site, would give the Cameroonian partners a unique ability or advantage that may also lead to new cooperations and projects.