More than 100 million people per year are affected by hydrological extremes, i.e. floods and droughts. Hydrological studies have investigated human impacts on droughts and floods, while conversely social studies have explored human responses to hydrological extremes. Yet, the dynamics resulting from their interplay, i.e. both impacts and responses, have remained poorly understood. Thus, current risk assessment methods do not explicitly account for these dynamics. As a result, while risk reduction strategies built on these methods can work in the short-term, they often lead to unintended consequences in the long-term. As such, this project aims to unravel the mutual shaping of society and hydrological extremes. A combined theoretical and empirical approach will be developed to uncover how the occurrence of hydrological extremes influences society’s wealth, institutions and population distribution, while, at the same time, society in turn alters the frequency, magnitude and spatial distribution of hydrological extremes via structural measures of water management and disaster risk reduction. To explore the causal mechanisms underlying this mutual shaping, this project will propose explanatory models as competing hypotheses about the way in which humans drive and respond to droughts and floods. These alternative explanations will be developed and tested through: i) empirical analysis of case studies, and ii) global investigation of numerous sites, taking advantage of the current unprecedented proliferation of worldwide datasets. By combining these different methods, this project is expected to address the gap of fundamental knowledge about the dynamics of risk emerging from the interplay of hydrological extremes and society.
Allosteric regulation of enzyme catalysis is widespread in nature and presents challenges and opportunities in synthetic biology. The enzyme ATP-phosphoribosyltransferase (ATPPRT) catalyses the first step in histidine biosynthesis, and is subject to complex allosteric inhibition by histidine. The short form of the enzyme, HisGS, is found in complex with a regulatory protein, HisZ. Such regulatory protein has a dual function: it allosterically enhances catalysis by HisGS, and it binds histidine and therefore mediates allosteric inhibition. The scientific aim of "DEAllAct" is to explore the design of a computational framework by combining state-of-the-art EVB/MM computational simulations and biophysical experimental studies to discover specific mutations at the protein-protein interface between HisGS and HisZ, that directly impact the transmission mechanism of the allosteric regulation. The fellow, Marina Corbella will carry out the project in Uppsala University under the supervision of Prof. Lynn Kamerlin who has extensive experience in computational chemistry and enzyme evolution. The first goal of "DEAllAct" is to elucidate the molecular details of the catalytic process of HisGS in the absence/presence of the regulatory protein HisZ via molecular dynamics simulations. Based on the information extracted from these simulations, a novel simulation tool will be developed to predict residues of key importance for binding interactions between the enzyme and the regulatory protein. Finally, the fellow will undergo a secondment at the University of St Andrews to test the hypothesis experimentally by introducing gain-of-function mutations on HisGS at the protein-protein interface to mimic the allosteric activation. Altogether, "DEAllAct" will provide the fellow with a highly competitive multidisciplinary profile by complementing her previous acquired expertise, putting her in a strong position to initiate her career as an independent and innovative research leader.
Virtually all terrestrial plants depend on symbiotic interactions with fungi. Arbuscular mycorrhizal (AM) fungi evolved over 450 million years ago, are obligate biotrophs and cannot complete their lifecycle without obtaining carbon from host roots. Mediating nutrient uptake and sequestering carbon in soil this symbiosis lie at the core of all terrestrial ecosystems. Plants on the other hand are facultative mycotrophs but under natural conditions all host roots are colonized as a result of multiple beneficial effects of AM fungi. In the symbiosis, both plants and fungi are promiscuous, forming interactions across individuals and species. In the absence of host-symbiont specificity and given their inability to discriminate among partners prior to interaction, evolutionary theory predicts that “free riders” would evolve and spread. Yet AM fungi remain evolutionary and ecologically successful. I propose that this is thanks to their unique genomic organization, a temporally dynamic heterokaryosis. Unlike other eukaryotes, AM fungi have no single nucleate stage in their life cycle, instead they reproduce asexually by forming large multinucleate spores. Genetic variation is high and nuclei can migrate and mix within extensive mycelial networks. My group has recently established a single nucleus genomics method to study genetic variation among nuclei within AM fungi. With this method I can resolve the extent of heterokaryosis in AM fungi and its temporal dynamics. I will study the emergence of “free riders” upon intra organismal segregation of genetically distinct nuclei during AM fungal adaptation to host. Further I will study how hyphal fusion and nuclear mixing counteract segregation to stabilize the symbiosis. The research program has great potential for novel discoveries of fundamental importance to evolutionary and environmental biology and will also contribute to agricultural practice and management of terrestrial ecosystems.