‘‘The states of health or disease are the expressions
of the success or failure experienced by the organism
in its efforts to respond adaptively to environmental
challenges.’’—Rene Dubos, 1965
Most organisms have an elaborate and complex immune system. While molecular and cellular mechanisms underlying immune responses have been worked out in relatively greater detail, understanding of its ecology & evolution is limited. We are therefore interested in tracking the evolutionary ecological history of various immune responses and associated selective parameters that have fundamental as well as considerable biomedical importance. We are primarily using experimental evolution in lab adapted tractable insect populations (e.g. flour beetles and fruit flies), life-history analysis, and genetic methods. Below, I broadly describe major research themes being pursued in my lab at Ashoka University—
Evolution in Aging, Infection and Health
Modern biological research is greatly equipped to tackle the question ‘how’, but often struggles when asked ‘why’. One such classic example is aging research. Research over the last century has established the physiological mechanisms of aging and its morbid symptoms such as chronic battle against infection, disease and death. But, it is unfortunate that we have very limited insights about why aging brings about such consequences. My lab at Ashoka University is trying to offer some clues, using our expertise in evolution and immunology. We think, that although aging is a complex phenomenon with multiple aspects, much of its features during later-life can largely be explained by deregulated immune responses. At the heart of our proposed hypothesis is natural selection, the key mechanism of evolution – with a steady decline in reproductive ability with age, natural selection can become too weak to effectively control immune responses in older individuals, producing excessive immune activation at an inappropriate level.
We have already tested some important ideas in a range of model insects (e.g. fruit flies, flour beetles and meal worm beetles) that share several similar immune features with humans and other higher organisms. Do animals always benefit from immune responses? In an important paper published in the Proceedings of the Royal Society B, we, for the first time, pointed out that mounting immune responses is not always beneficial – instead, the net health impact of immune responses depend on when and how they are activated (i.e. individual’s age). For example, young individuals injected with bacterial cell components mounted an immune response that damaged their vital organs and resulted in early aging with increased death rate, suggesting long-lasting effects of an early-life infection. Whereas, reducing the immune response extended their life. Similarly, older individuals injected with a live pathogen lived longer, only if their immune response was suppressed. We now reason that similar mechanisms could also operate in other organisms, as aging is an integral feature of most multi-cellular life, including humans.
However, most things remain to be tested. To find more experimental evidence for our hypothesis, my group at Ashoka University is now directly testing the evolutionary outcomes of excessive immune responses during ageing. Pavan and Saubhik Sarkar, two of my PhD students, are using experimental evolution, a powerful tool to observe evolutionary processes in the laboratory animal models, and evolutionary physiology as approaches to address these issues. Since tracking evolution in higher organisms, including humans, is difficult with their complex immune system and long generation cycle, our group uses faster-reproducing insect populations with relatively simple immune system that provide an excellent opportunity to tease apart fundamental evolutionary processes and their impacts on age-related physiological processes. With a constant age-specific rise in autoimmune inflammatory diseases such as diabetes, multiple sclerosis and arthritis in human populations across the globe, our research aims to provide critical breakthroughs in our fundamental understanding of ageing.
Evolution of immune memory-like responses in insects
A longstanding belief in immunology is that insects lack memory and specificity in their immune response because they do not have the lymphocytes and functional antibodies that are responsible for the acquired immunity in vertebrates. Despite this, growing evidence suggests that low doses of pathogens may prime the immune response in insects (with relative simple innate immunity), reducing the risk and severity of infection by the same pathogen in the same developmental stage, across life stages, or to offspring (see Khan et al. 2016, Ecology and Evolution; Khan et al. 2017b, Proceedings B). Hence, an emerging question on insect immunity is – Are they really simple? or, we are just underestimating their potential. My lab is thus interested in tracking how different forms of insect immune memory evolve in both laboratory adapted and wild populations, as a function of changing pathogen environment. We also expect to generate some powerful insights into their underlying mechanisms soon.
Evolution of adult traits in response to chronic environmental stress
As a curious biologist, I am also interested in how the environmental conditions can impact our life. For instance, crowding (too many individuals) can intensify competition for food, reducing the nutritional intake. It can also increase the exposure to pathogens and toxic metabolic waste products, leading to poor hygienic conditions. How does an organism counter such poor conditions then? One possibility is that under these stressful circumstances, organisms can alter reproductive investments (producing lower number of offspring) to reduce the population size. My recent work (with Deepa Agashe’s Lab at National Centre for Biological Sciences), published in a prominent scientific journal American Naturalist, not only provides an interesting example but also supports the hypothesis. Using global pest species red flour beetles; we demonstrated that they could significantly reduce their reproductive performance in response to high female numbers in populations. We further discovered that the entire process is chemically controlled. In a dense population, female beetles release toxic ‘quinone’ secretions from their body to communicate to other members so that they all can re-adjust the reproductive rate to avoid competition for food. This is also a rare example where we could find a chemical cause for a fundamental biological problem.
However, biological problems are rarely simple. As an example, same quinones that are used by females for chemical communication under crowding are also potent antimicrobial agents since they can hinder pathogen growth in their surrounding environment. Therefore, the open question that we have is complex and multi-layered – is quinone production a response shaped by evolution to avoid crowding, or to keep the environment free from pathogens, or both? Once again, running long-term evolution experiments may have the answer. Basabi Bagchi, another PhD student in my lab, with several Ashoka undergrads, is testing different hypotheses on beetle quinones and their relevance to both population size and pathogen inhibition.
We have secured generous funding from Ashoka University and SERB-DST to support these projects