ERC FUNDED PROJECTS

Highly excited electronic states of small atmospheric molecules play an important, but as yet little explored, role in the reactivity, and in the evolution of plasmas, including the Aurora Borealis, in the upper atmosphere of the Earth. Processes involving these highly excited states are very challenging to investigate theoretically because of the high density of states close to the ionization limits where they lie. Therefore, experimental input is essential for the identification of the reaction and decay mechanisms, and the quantum states of importance in future studies. However, experimental techniques that can be exploited to provide this input have only become available very recently. These techniques permit gas-phase molecular samples in these highly excited states to be confined in traps for sufficient lengths of time (e.g. 1 ms – 10 ms) for detailed studies to be performed in a controlled laboratory environment. They include resonance-enhanced and non-resonance-enhanced multiphoton excitation of long-lived high angular momentum Rydberg states of small molecules, and chip-based devices for efficiently decelerating, transporting and trapping these samples. With the support of this Consolidator Grant a new experimental research program will be developed in the Department of Physics and Astronomy at University College London involving laboratory based studies of (1) inelastic scattering processes, and (2) the decay mechanisms of gas-phase atmospheric molecules, including N2, O2 and NO, and their constituent atoms, in high Rydberg states. The planned experiments will be directed toward understanding the effects of static and time-dependent electric and magnetic fields, and blackbody radiation fields on slow dissociation processes that occur in highly excited states of N2, O2 and NO, investigations of collisional energy transfer processes, and studies of the role that these excited electronic states play in the evolution and reactivity of atmospheric plasmas incl

1 985 553 €

Start date: 2016-06-01, End date: 2021-05-31

Endosymbiosis is a key phenomenon that has played a critical role in shaping biological diversity, driving gene transfer and generating cellular complexity. During the process of endosymbiosis, one cell is integrated within another to become a critical component of the recipient, changing its characteristics and allowing it to chart a distinct evolutionary trajectory. Endosymbiosis was fundamentally important to the origin and evolution of eukaryotic cellular complexity, because an endosymbiotic event roots the diversification of all known eukaryotes and endosymbiosis has continually driven the diversification of huge sections of the eukaryotic tree of life. Little is known about how nascent endosymbioses are established or how they go on to form novel cellular compartments known as endosymbiotic organelles. Paramecium bursaria is a single celled protist that harbours multiple green algae within to form a phototrophic endosymbiosis. This relationship is nascent as the partners can be separated, grown separately, and the endosymbiosis reinitiated. This project will identify, for the first time, the gene functions that enable one cell to incubate another within to form a stable endosymbiotic interaction. To identify and explore which host genes control endosymbiosis in P. bursaria we have developed RNAi silencing technology. In the proposed project we will conduct genome sequencing, followed by a large-scale RNAi knockdown screening experiment, to identify host genes that when silenced perturb the endosymbiont population. Having identified candidate genes, we will investigate the localisation and function of the host encoded proteins. This project will significantly change our current understanding of the evolutionary phenomenon of endosymbiosis by identifying the cellular adaptations that drive these interactions, advancing our understanding of how these important moments in evolution occur and how core cellular systems can diversify in function.

2 602 483 €

Start date: 2019-06-01, End date: 2024-05-31

Genetic heterogeneity and complexity are hallmarks of metastatic solid tumors and therapy resistance inevitably develops upon treatment with cytotoxic drugs or molecular targeted therapies. Cholangiocarcinoma (CCC, or bile duct cancer) represents the second most frequent primary liver tumor and has emerged as a health problem with sharply increasing incidence rates, in particular of intrahepatic CCC (ICC). The reason for increased CCC incidence remains unclear, but influences of western lifestyle and a resulting altered hepatic metabolism have been discussed. Surgical resection represents the only curative option for the treatment of CCC, however, many tumors are irresectable at the time of diagnosis. CCC represents a highly aggressive and metastatic tumor type and currently no effective systemic therapy regimen exists. The overall molecular mechanisms driving CCC formation and progression remain poorly characterized and it thus becomes clear that a detailed molecular characterization of cholangiocarcinogenesis and the identification of robust therapeutic targets for CCC treatment are urgently needed. Taking advantage of our strong expertises in chimaeric (mosaic) liver cancer mouse models and stable in vivo shRNA technology, we here propose a comprehensive and innovative approach to i) dissect molecular mechanisms of cholangiocarcinogenesis, with a particular emphasis on Kras driven ICC development from adult hepatocytes and oncogenomic profiling of ICC metastasis, ii) to employ direct in vivo shRNA screening to functionally identify new therapeutic targets for CCC treatment and iii) to characterize the role of the gut microbiome for CCC progression and metastasis. We envision this ERC-funded project will yield important new insights into the molecular mechanisms of CCC development, progression and metastasis. As our work comprises direct and functional strategies to identify new vulnerabilities in CCC, the obtained data harbor a very high translational potential.

1 998 898 €

Start date: 2015-09-01, End date: 2020-08-31

"More than 150 years after the publication of Charles Darwin’s The Origin of Species, the identification of the processes that govern the emergence of novel species remains a fundamental problem to biology. Why is it that some groups have diversified in a seemingly explosive manner, while others have lingered unvaried over millions of years? What are the external factors and environmental conditions that promote organismal diversity? And what is the molecular basis of adaptation and diversification? A key to these and related questions is the comparative study of exceptionally diverse yet relatively recent species assemblages such as Darwin’s finches, the Caribbean anole lizards, or the hundreds of endemic species of cichlid fishes in the East African Great Lakes, which are at the center of this proposal. More specifically, I intend to conduct the so far most thorough examination of a large adaptive radiation, combining in-depth eco-morphological assessments and whole genome sequencing of all members of a cichlid species flock. To this end, I plan to (i) sequence the genomes and transcriptomes of several specimens of each cichlid species from Lake Tanganyika to examine genetic and transcriptional diversity; (ii) apply stable-isotope and stomach-content analyses in combination with underwater transplant experiments and transect surveys to quantitate feeding performances, habitat preferences and natural-history parameters; (iii) use X-ray computed tomography to study phenotypic variation in 3D; and (iv) examine fossils from existing and forthcoming drilling cores to implement a time line of diversification in a cichlid adaptive radiation. This project, thus, offers the unique opportunity to test recent theory- and data-based predictions on speciation and adaptive radiation within an entire biological system – in this case the adaptive radiation of cichlid fishes in Lake Tanganyika."

1 999 238 €

Start date: 2014-03-01, End date: 2019-02-28