ERC FUNDED PROJECTS

"Recently through de novo peptide design, we have discovered and presented a new protein structure. This is an all-parallel, 6-helix bundle with a continuous central channel of 0.5 – 0.6 nm diameter. We posit that this is one of a broader class of protein structures that we call the alpha-helical barrels. Here, in three Work Packages, we propose to explore these structures and to develop protein functions within them. First, through a combination of computer-aided design, peptide synthesis and thorough biophysical characterization, we will examine the extents and limits of the alpha-helical-barrel structures. Whilst this is curiosity driven research, it also has practical consequences for the studies that will follow; that is, alpha-helical barrels made from increasing numbers of helices have channels or pores that increase in a predictable way. Second, we will use rational and empirical design approaches to engineer a range of functions within these cavities, including binding capabilities and enzyme-like activities. Finally, and taking the programme into another ambitious area, we will use the alpha-helical barrels to template other folds that are otherwise difficult to design and engineer, notably beta-barrels that insert into membranes to render ion-channel and sensor functions."

2 467 844 €

Start date: 2014-02-01, End date: 2019-01-31

Increasing crop yield to feed the world is a grand challenge of the 21st century but it is hampered by diseases caused by filamentous plant pathogens. The arms race between pathogen and plant demands constant adjustment of crop germplasm to tackle emerging pathogen races with new virulence features. To date, most crop disease resistance has relied on specific resistance genes that are effective only against a subset of races. We cannot solely rely on classical resistance genes to keep ahead of the pathogens. There is an urgent need to develop approaches based on knowledge of the pathogen’s Achilles heel: core plant processes that are required for pathogen colonization. Our hypothesis is that disease resistance based on manipulation of host accessibility processes has a higher probability for durability, and is best identified using a broad host-range pathogen. I will employ the filamentous pathogen Phytophthora palmivora to mine plant alleles and unravel host processes providing microbial access in roots and leaves of monocot and dicot plants. In Aim 1 I will utilize plant symbiosis mutants and allelic variation to elucidate general mechanisms of colonization by filamentous microbes. Importantly, allelic variation will be studied in economically relevant barley and wheat to allow immediate translation into breeding programs. In Aim 2 I will perform a comparative study of microbial colonization in monocot and dicot roots and leaves. Transcriptional profiling of pathogen and plant will highlight common and contrasting principles and illustrate the impact of differential plant anatomies. We will challenge our findings by testing beneficial fungi to assess commonalities and differences between mutualist and pathogen colonization. We will use genetics, cell biology and genomics to find suitable resistance alleles highly relevant to crop production and global food security. At the completion of the project, I expect to have a set of genes for resistance breeding.

1 991 054 €

Start date: 2015-09-01, End date: 2021-08-31

This proposal is focused in the areas of chemical medicine and chemical biology with the key drivers being the discovery and development of new materials that have practical functionality and application. The project will enable the fabrication of thousands of three-dimensional “smart-polymers” that will allow: (i). The precise and controlled release of drugs upon the addition of either a small molecule trigger or in response to disease, (ii). The discovery of materials that control and manipulate cells with the identification of scaffolds that provide the necessary biochemical cues for directing cell fate and drive tissue regeneration and (iii). The development of new classes of “smart-polymers” able, in real-time, to sense and report bacterial contamination. The newly discovered materials will find multiple biomedical applications in regenerative medicine and biotechnology ranging from 3D cell culture, bone repair and niche stabilisation to bacterial sensing/removal, while offering a new paradigm in drug delivery with biomarker triggered drug release.

2 310 884 €

Start date: 2014-11-01, End date: 2019-10-31

Over the past decade, the media, international organisations, as well as policy-making bodies have voiced increasing concern about a growing overlap between the criminal and political spheres in South Asia. Many 'criminal politicians' are accused not simply of embezzlement, but of burglary, kidnapping and murder, so that the observed political landscape emerges not only as a 'corrupt', but also a highly violent sphere. This project is a collaborative and cross-national ethnographic study of the criminalisation of politics in India, Pakistan and Bangladesh. Bringing together local-level investigation, surveys and historical analysis, the project will produce comprehensive political ethnographies in sixteen sites across the subcontinent, providing empirical material and theoretical directives for further charting of the virtually unexplored terrain of extra-legal muscular politics in the region. Central to the proposed programme of research are the following interrelated objectives: 1) To further develop the method of collaborative political ethnography by designing, collecting and producing case studies which will allow us to write thematically across sites; 2) To generate policy relevant research in the fields of security, conflict, democracy and development; 3) To produce capability by forging an international network of scholars on issues related to democratisation, violence, crime and support the work and careers of the project's 4 Post-docs. The study capitalises on previous research and skills of the PI in the cross-cultural study of democracy and muscular politics in the global South. All members of the research team have expertise in ethnographic research in the difficult spheres of criminal politics, informal economies, and political violence and are hence well and sometimes uniquely equipped to pursue this challenging research thematic.

1 200 000 €

Start date: 2012-03-01, End date: 2016-02-29