Understanding Human Immunity from Studying Fish

Harnessing a complete map of genetic variations in immunity to fight against parasites and diseases

Research in epidemiology has iconically relied on the white lab mouse as a means to explore the immune system of a species believed to accurately reflect that of human beings; however, mice are proving to be an insufficient model on their own. Experimentation with mice has overlooked some important features of immune function, such as the fact that B cells can ingest pathogens directly, which was instead discovered in recent studies of fish immunity. Dr. Daniel Bolnick, of The University of Texas at Austin, leads investigations in fish because of prominent similarities both in genes shared between fish and humans and the similar parasites and viruses that we face. His group reaches beyond the conventional "break it and see what happens" technique commonly employed by immunologists who search for natural mutations (or induce mutations) to see how genetic changes undermine immune function. Instead, Dr. Bolnick takes advantage of evolutionary history to find genes with different beneficial functions. Fish from different habitats have evolved unique immunological solutions to their particular native parasites. By surveying different habitats, he can find immune genes used in beneficial adaptations to diverse parasite conditions. This approach should identify immune genes that, when changed, provide new beneficial functions, in contrast to the traditional search for genes that can break immune functions. The genes that natural selection favors to evade parasites may be more useful in designing anti-parasite therapies, and may provide a more accurate picture of the human immune system and its challenges.

As the only investigator to be awarded both the Dobzhansky Prize in evolution and the Mercer Award in ecology, Dr. Bolnick uniquely combines both evolutionary biology and ecology in his research on immune function. As a result of this work, he is also one of the only evolutionary biologists to win a research fellowship with the Howard Hughes Medical Institute. Additionally, Dr. Bolnick has received nine other international awards for his work. In a research society bent on curing illnesses caused by viruses and microbes prevalent in Western countries, Dr. Bolnick's group is instead focused on studying immune resistance to larger parasites, such as tapeworms, that more commonly attack communities in developing countries where health and sanitation systems endure lower standards. Similarly to how immunology research has yielded effective vaccines against the influenza virus, understanding genetic susceptibility to tapeworms, roundworms, nematodes, and flukes could lead to health treatments that would protect a large portion of humanity from their most prominent diseases. With such diseases eliminated, life expectancy for communities affected by these parasites would rise dramatically.

Current research includes the following projects:

  • Identifying Parasite Genetics: Understanding immune responses against parasites often requires knowing the exact genetic traits of the parasite in question. There is substantial genetic variation even within parasite species, and Dr. Bolnick's team has found that this genetic variation is important to understand infection success. Certain parasite strains are more successful at infecting certain host lineages. By mapping the parasite genes that cause such variation, we eventually hope to be able to develop individualized therapies that are tailored to individual host and parasite lineages.

  • Mapping Genetic Variation in Immunity: Whereas traditional research has often relied on damaging gene mutations to study immune systems, Dr. Bolnick is reaching to fill in the genetic map of immunity by studying mutations which have beneficial effects in particular parasite settings. Instead of only focusing on artificially mutated genes or ones that cause illness, Dr. Bolnick's research provides a more comprehensive outlook on the naturally existing variation in immunity genes to explain the different approaches to how individuals in a population effectively fight parasites and diseases. Studying populations of species in various environments allows for natural selection to point out the most important immunological genes, instead of random guess-and-checking.

  • Vertebrate Immunity in the Wild: Observing how individuals and their immune systems react to daily conditions of stress in the wild delivers a more useful idea of realistic immune function than studies limited to pristine laboratory settings with mice. Dr. Bolnick's research has already found that immune profiles of individuals are altered by changing their natural environment, which is the first step in determining how temperature, diet, and social interaction can drive immune defense against parasites and diseases. This may be particularly relevant to studying diseases in wild or farmed animals in the face of environmental change such as global warming.

  • Expanding the Understanding of Immunity Evolution to 100 Vertebrates: Mice are the mainstay of immunological research, but how good a proxy are they, really, for human immunity? Is it wise to invest all our research effort in one tool? Dr. Bolnick argues that we should develop a diversified portfolio of species for immunological research. Different vertebrate species may each be best suited to reveal some different facet about human immunity. To diversify immunology, Dr. Bolnick is using the leading edge of DNA- and RNA-sequencing technology to gain a better understanding of immunity in a wider variety of species beyond the standard set of lab animals. He aims to begin by describing the major types of immune cells, and their gene profiles, in a diverse sample of 100 vertebrates. Doing so may identify previously unknown immune cell types, genes, and pathways.

Bio

Dr. Bolnick holds a natural fascination for biological diversity that bloomed in the early years of his childhood spent in Indonesia. What began as fun explorations with his parents visiting reefs, jungles, and mountains soon led to a passion for nature and the conservation of its abundant diversity. In his last year of high school, Dr. Bolnick's family moved to Zambia, Africa where he was able to assist botanists and ornithologists in their research and discover a personal wish to study nature on his own. Throughout his time at Williams College, Dr. Bolnick transformed his passion into research, which he actively pursued both at home and in Africa. After graduation, he spent two years teaching advanced high school biology in Tanzania for the U.S. Peace Corps.

Upon starting his Ph.D. at UC Davis, Dr. Bolnick found a niche of research that was especially captivating to him: if natural selection is supposed to weed out the genes of individuals less likely to survive and reproduce, then why is there still so much variation in the surviving populations of species we see today? Whereas many evolutionary biologists had their spotlight on the origin of new species, Dr. Bolnick decided to explore the natural diversity within existing species. His Ph.D. degree and postdoctoral research at UC Davis explored the ecological forces that help sustain genetic diversity within species. Moving on to the University of Texas in 2004, he became fascinated by immunology and parasites and chose to shift fields, applying his evolutionary and ecological expertise to provide a new perspective on immunity.

Dr. Bolnick's undergraduate teaching focuses on training future K-12 science and math teachers how to interpret and conduct scientific research. He also mentors many undergraduates and current and future teachers in his research lab. This is rewarding because it helps ensure that science teachers actually understand the scientific method underpinning their work. To illustrate, a recent graduate from his lab immediately landed a job teaching biology at a Texas public high school. On her first day of the job, her new students, who until recently had a teacher without a science degree, asked her whether she "actually knew science." When she responded that she had actually done independent research in a parasitology and immunology lab, the room erupted in cheers. This vignette highlights the point that Dr. Bolnick's research plays an important role in training future educators, as well as in advancing the frontiers of knowledge about disease and immunity.

Website: http://web.biosci.utexas.edu/bolnick_lab/home.html

Awards

David Starr Jordan Prize for Innovative Contributions to the Study of Evolution, Ecology, Population or Organismal Biology, 2014

Cornell, Stanford, and Indiana University

College of Biological Sciences Young Alumni Award, 2011

University of California, Davis

Secretary, 2010-2012

American Society of Naturalists

Stand Up for Science Award, 2009

Texas Freedom Network

Early Career Scientist, 2009-2015

Howard Hughes Medical Institute