ERC FUNDED PROJECTS

Recent technological advances in optical microscopy have vastly broadened the possibilities for applications in the biomedical sciences. Fluorescence microscopy is the central tool for investigation of molecular structures and dynamics that take place in the cellular and tissue environment. Coupled with progress in labeling methods, these microscopes permit observation of biological structures and processes with unprecedented sensitivity and resolution. This work has been enabled by the engineering development of diverse optical systems that provide different capabilities for the imaging toolkit. All such methods rely upon high fidelity optics to provide optimal resolution and efficiency, but they all suffer from aberrations caused by refractive index variations within the specimen. It is widely accepted that in many applications this fundamental problem prevents optimum operation and limits capability. Adaptive optics (AO) has been introduced to overcome these limitations by correcting aberrations and a range of demonstrations has shown clearly its potential. Indeed, it shows great promise to improve virtually all types of research or commercial microscopes, but significant challenges must still be met before AO can be widely implemented in routine imaging. Current advances are being made through development of bespoke AO solutions to individual imaging tasks. However, the diversity of microscopy methods means that individual solutions are often not translatable to other systems. This proposal is directed towards the creation of theoretical and practical frameworks that tie together AO concepts and provide a suite of scientific tools with broad application. This will be achieved through a systems approach that encompasses theoretical modelling, optical engineering and the requirements of biological applications. Additional outputs will include practical designs, operating protocols and software algorithms that will support next generation AO microscope systems.

3 234 789 €

Start date: 2016-09-01, End date: 2021-08-31

This project focuses on two questions about host/parasite interactions: how do biotrophic plant pathogens suppress host defence? and, what is the basis for pathogen specialization on specific host species? A broadly accepted model explains resistance and susceptibility to plant pathogens. First, pathogens make conserved molecules ( PAMPS ) such as flagellin, that plants detect via cell surface receptors, leading to PAMP-Triggered Immunity (PTI). Second, pathogens make effectors that suppress PTI. Third, plants carry 100s of Resistance (R) genes that detect an effector, and activate Effector-Triggered Immunity (ETI). One effector is sufficient to trigger resistance. Albugo candida (Ac) (white rust) strongly suppresses host defence; Ac-infected Arabidopsis are susceptible to pathogen races to which they are otherwise resistant. Ac is an oomycete, not a fungus. Arabidopsis is resistant to races of Ac that infect brassicas. The proposed project involves three programs. First ( genomics, transcriptomics and bioinformatics ), we will use next-generation sequencing (NGS) methods (Solexa and GS-Flex), and novel transcriptomics methods to define the genome sequence and effector set of three Ac strains, as well as carrying out >40- deep resequencing of 7 additional Ac strains. Second, ( effectoromics ), we will carry out functional assays using Effector Detector Vectors (Sohn Plant Cell 19:4077 [2007]), with the set of Ac effectors, screening for enhanced virulence, for suppression of defence, for effectors that are recognized by R genes in disease resistant Arabidopsis and for host effector targets. Third, ( resistance diversity ), we will characterize Arabidopsis germplasm for R genes to Ac, both for recognition of Arabidopsis strains of Ac, and for recognition in Arabidopsis of effectors from Ac strains that infect brassica. This proposal focuses on Ac, but will establish methods that could discover new R genes in non-hosts against many plant diseases.

2 498 923 €

Start date: 2009-01-01, End date: 2014-06-30

The ability of positrons to annihilate with electrons, producing characteristic gamma rays, gives them important use in medicine via positron-emission tomography (PET), diagnostics of industrially-important materials, and in elucidating astrophysical phenomena. Moreover, the fundamental interactions of positrons and positronium (Ps) with atoms, molecules and condensed matter are currently under intensive study in numerous international laboratories, to illuminate collision phenomena and perform precision tests of fundamental laws. Proper interpretation and development of these costly and difficult experiments requires accurate calculations of low-energy positron and Ps interactions with normal matter. These systems, however, involve strong correlations, e.g., polarisation of the atom and virtual-Ps formation (where an atomic electron tunnels to the positron): they significantly effect positron- and Ps-atom/molecule interactions, e.g., enhancing annihilation rates by many orders of magnitude, and making the accurate description of these systems a challenging many-body problem. Current theoretical capability lags severely behind that of experiment. Major theoretical and computational developments are required to bridge the gap. One powerful method, which accounts for the correlations in a natural, transparent and systematic way, is many-body theory (MBT). Building on my expertise in the field, I propose to develop new MBT to deliver unique and unrivalled capability in theory and computation of low-energy positron and Ps interactions with atoms, molecules, and condensed matter. The ambitious programme will provide the basic understanding required to interpret and develop the fundamental experiments, antimatter-based materials science techniques, and wider technologies, e.g., (PET), and more broadly, potentially revolutionary and generally applicable computational methodologies that promise to define a new level of high-precision in atomic-MBT calculations.

1 318 419 €

Start date: 2019-02-01, End date: 2024-01-31

This proposal outlines a plan to combine Charge Couple Device (CCD) camera technologies with two-phase Liquid Argon Time Projection Chambers (LAr TPCs) utilising THick Gas Electron Multipliers (THGEMs) to evolve a next generation neutrino detector. This will be an entirely new readout option, and will open the prospect of revolutionary discoveries in fundamental particle physics. Furthermore, the Compton imaging power of this technology will be developed, which will have diverse applications in novel medical imaging techniques and detection of concealed nuclear materials. Colossal LAr TPCs are the future for long-baseline-neutrino-oscillation physics around which the international neutrino community is rallying, with the common goal of discovering new physics beyond the Standard Model, which holds the key to our understanding of phenomena such as dark matter and the matter-antimatter asymmetry. I have successfully provided a first demonstration of photographic capturing of muon tracks and single gammas interacting in the Liverpool 40 l LAr TPC using a CCD camera and THGEM. I propose an ambitious project of extensive research to mature this innovative LAr optical readout technology. I will construct a 650 l LAr TPC with integrated CCD/THGEM readout, capable of containing sufficient tracking information for full development and characterisation of this novel detector, with the goal of realising this game-changing technology in the planned future giant LAr TPCs. Camera readout can replace the current charge readout technology and associated scalability complications, and the excellent energy thresholds will enhance detector performance as well as extend research avenues to lower energy fundamental physics. Also, I will explore the Compton imaging capability of LAr CCD/THGEM technology; the superiority of the energy threshold and spatial resolution of this system can offer significant advancement to medical imaging and the detection of concealed nuclear materials.

1 837 911 €

Start date: 2016-03-01, End date: 2021-02-28