ERC FUNDED PROJECTS

"The twin concepts of sustainability and conservation that are so pivotal within current debates regarding economic development and biodiversity protection both contain an inherent temporal dimension, since both refer to the need to balance short-term gains with long-term resource maintenance. Proponents of resilience theory and of development based on ‘indigenous knowledge’ have thus argued for the necessity of including archaeological, historical and palaeoenvironmental components within development project design. Indeed, some have argued that archaeology should lead these interdisciplinary projects on the grounds that it provides the necessary time depth and bridges the social and natural sciences. The project proposed here accepts this logic and endorses this renewed contemporary relevance of archaeological research. However, it also needs to be admitted that moving beyond critiques of the misuse of historical data presents significant hurdles. When presenting results outside the discipline, for example, archaeological projects tend to downplay the poor archaeological visibility of certain agricultural practices, and computer models designed to test sustainability struggle to adequately account for local cultural preferences. This field will therefore not progress unless there is a frank appraisal of archaeology’s strengths and weaknesses. This project will provide this assessment by employing a range of established and groundbreaking archaeological and modelling techniques to examine the development of two east Africa agricultural systems: one at the abandoned site of Engaruka in Tanzania, commonly seen as an example of resource mismanagement and ecological collapse; and another at the current agricultural landscape in Konso, Ethiopia, described by the UN FAO as one of a select few African “lessons from the past”. The project thus aims to assess the sustainability of these systems, but will also assess the role archaeology can play in such debates worldwide."

1 196 701 €

Start date: 2014-02-01, End date: 2018-01-31

Graphene – a one atom thin material – has the potential to act as a sensor, primarily the surface and the edges of graphene. This proposal aims at exploring new biosensing routes by exploiting the unique surface and edge chemistry of graphene.

1 499 996 €

Start date: 2014-05-01, End date: 2019-04-30

"Although protein dynamics plays an essential role in function, it is rarely considered explicitly in current structure-based approaches to drug design. Here I propose the computer-aided design of ligands by modulation of protein dynamics, or equivalently, protein structural ensembles. The detailed understanding of ligand-induced perturbations of protein dynamics that will result from this study is crucial not just to accurately predicting binding affinities and tackling ""undruggable"" targets, but also to understanding protein allostery. Three major aims will be pursued during this project. First, I will combine concepts from chemoinformatics and non-equilibrium thermodynamics to detect cryptic ""druggable"" small molecule binding sites in computed structural ensembles. New computational methods will be developed to predict how binding at these putative sites is likely to influence protein function. This will enable rational approaches to allosteric control of protein function. Second, new classes of non-equilibrium sampling algorithms will be developed to improve by 2-3 orders of magnitude the speed of computation of protein/ligand structural ensembles by molecular simulations. This will enable routine consideration of protein flexibility in ligand optimisation problems. Third, I will address with the above methods a frontier problem in molecular recognition: the rational design of protein isoform-specific ligands. To achieve this goal, I will integrate computation with experiments and focus efforts on the therapeutically relevant cyclophilin protein family. Experimental work will involve the use of purchased or custom-synthesized competitive and allosteric ligands in enzymatic assays, calorimetry and crystal structure analyses. Overall, this project proposes fundamental advances in our ability to quantify and engineer protein-ligand interactions, therefore expanding opportunities for the development of future small molecule therapeutics."

1 382 202 €

Start date: 2013-12-01, End date: 2018-11-30

Hydrogen produced by sunlight is a very promising, environmentally-friendly energy source as an alternative for increasingly scarce and polluting fossil fuels. Since the discovery of hydrogen production by photocatalytic water dissociation on a titanium dioxide (TiO2) electrode 40 years ago, much research has been aimed at increasing the process efficiency. Remarkably, insights into how water is bound to the catalyst and into the dynamics of the photodissociation reaction, have been scarce up to now, due to the lack of suitable techniques to interrogate water at the interface. The aim of this proposal is to provide these insights by looking at specifically the molecules at the interface, before, during and after their photo-reaction. With the surface sensitive spectroscopic technique sum-frequency generation (SFG) we can determine binding motifs of the ~monolayer of water at the interface, quantify the heterogeneity of the water molecules at the interface and follow changes in water molecular structure and dynamics at the interface during the reaction. The structure of interfacial water will be studied using steady-state SFG; the dynamics of the water photodissociation will be investigated using pump-SFG probe spectroscopy. At variable delay times after the pump pulse the probe pulses will interrogate the interface and detect the reaction intermediates and products. Thanks to recent developments of SFG it should now be possible to determine the structure of water at the TiO2 interface and to unravel the dynamics of the photodissocation process. These insights will allow us to relate the interfacial TiO2-water structure and dynamics to reactivity of the photocatalyst, and to bridge the gap between the fundamentals of the process at the molecular level to the efficiency of the photocatalys. The results will be essential for developing cheaper and more efficient photocatalysts for the production of hydrogen.

1 498 800 €

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