ERC FUNDED PROJECTS

The key organizing principles that characterize neuronal systems include asymmetric, parallel, and topographic connectivity of the neural circuits. The main aim of my research is to elucidate the key principles underlying functional development of neural circuits by focusing on those organizing principles. I choose mouse visual system as my model since it contains all of these principles and provides sophisticated genetic tools to label and manipulate individual circuit components. My research is based on the central hypothesis that the mechanisms of brain development cannot be fully understood without first identifying individual functional cell types in adults, and then understanding how the functions of these cell types become established, using cell-type-specific molecular and synaptic mechanisms in developing animals. Recently, I have identified several transgenic mouse lines in which specific cell types in a visual center, the superior colliculus, are labeled with Cre recombinase in both developing and adult animals. Here I will take advantage of these mouse lines to ask fundamental questions about the functional development of neural circuits. First, how are distinct sensory features processed by the parallel topographic neuronal pathways, and how do they contribute to behavior? Second, what are the molecular and synaptic mechanisms that underlie developmental circuit plasticity for forming parallel topographic neuronal maps in the brain? Third, what are the molecular mechanisms that set up spatially asymmetric circuit connectivity without the need for sensory experience? I predict that my insights into the developmental mechanism of asymmetric, parallel, and topographic connectivity and circuit plasticity will be instructive when studying other brain circuits which contain similar organizing principles.

1 500 000 €

Start date: 2015-04-01, End date: 2020-03-31

Domesticated crops hardly resemble their wild ancestors, and often trade higher yield in artificially optimized conditions for lower performance in fluctuating environments. Leafcutter ants (genus Atta) provide fascinating parallels with human farmers, harvesting fresh vegetation used as compost to produce domesticated fungal crops that feed massive societies with millions of workers. However, while human agricultural systems are imperiled by rapid global changes, leafcutter ants have managed to grow one type of cultivar from Texas to Argentina, thriving across extreme rainfall and temperature gradients and across diverse climates over millions of years. However, the eco-physiological mechanisms governing this farming resiliency are poorly understood. I propose a new in vitro mapping paradigm to visualize the niche requirements of fungal cultivars. Creating multidimensional landscapes of nutrient availability (e.g. protein, carbohydrates, Na, P) and environmental stress (e.g. temperature, moisture, plant toxins, crop pathogens) I will answer three main questions: 1) What genes and biochemical pathways shape cultivar performance across interacting gradients of nutrition and stress? 2) Do colonies harvest substrates to navigate nutritional contours of cultivar performance maps and avoid production tradeoffs? 3) Do locally adaptive cultivar traits shape the performance of farming societies across regional ecological gradients, and over 60 million years of co-evolutionary crop domestication by farming ants? My cutting-edge approach will deliver transformative advances to the field of eco-physiology, enabling seamless integration between field and laboratory experiments, and providing new ways to visualize evolutionary mechanisms across levels of biological organization from genes to symbiotic partnerships, and from within diverse farming assemblages to across populations spanning entire continents.

1 427 741 €

Start date: 2018-02-01, End date: 2023-01-31

Background Lethal epidemics like the Black Death have killed millions of people and must pose an extreme selective pressure on any genetic variant that confers disease protection. Therefore, such epidemics have been hypothesized to play a key role in the evolution of humans. To what extent this is true, is a fundamental question of wide interest. Yet, it remains unanswered, in part due to limitations of the current methods to detect signatures of selection. Objectives I wish to accomplish three linked goals with the proposed project. The first goal is to develop new statistical methods for detecting signatures of adaptive natural selection driven by lethal epidemics. The second goal is to use these new methods to investigate the role of epidemics in recent human evolution by applying them to genetic data from several recent epidemics. The third goal is to gain insights into mechanisms that protect against infectious disease via the identification of genetic variants that have been under selection because they confer disease protection. Methods To reach these goals, extensive simulations will be performed to carefully characterize the genetic signatures of adaptive selection acting on a protective genetic variant during an epidemic. Then new statistical methods that can detect these signatures will be developed. Next, the new methods will be applied to several real datasets, including one from a recent Ebola epidemic. Finally, all signatures of selection detected in these real datasets will be further investigated. Expected outcome and importance This project will deliver new statistical methods that will move the field of selection studies a substantial step beyond the state-of-the-art by filling an important methodological gap. It will also yield key insights into the role of epidemics in recent evolutionary history. Finally, it has the potential to provide new knowledge on the genetics of disease resistance that could help prevent future lethal epidemics.

1 499 600 €

Start date: 2019-01-01, End date: 2023-12-31