The project aims to develop techniques that can accurately detect and measure carbon black concentrations in the atmosphere, in the smallest and least expensive possible manner. Particle matter and carbon black are some of the most important atmospheric pollutant, and are also important in number of manufacturing processes. Understanding the physics of how to measure particulate matter in an accurate and simple manner will pave the way to bring down the costs of these devices from tens of thousands to under a thousand pounds will enable cities and industrial sites to have a much better method for controlling nanoparticle formation, emission and transport. The initial part of the project will consider the miniaturisation of photoacoustic spectroscopy for carbon black detection, using conventional and MEMS techniques. Pending the outcome of the preliminary calculations and tests, we will pursue the development of the prototype and proceed with calibration, or pursue an alternative technique currently under way in the lab, based on UV charging and electrostatic methods. The research will have impacts in EPSRC's mission across aerosol fluid mechanics, nanoparticle and nanopowder detection, and combustion engineering.

Rebuilding the Cavendish Laboratory will deliver a state-of-the-art physics laboratory and enhance its unique status as one of the world's premier laboratories. The new, expanded Laboratory will provide leadership and support for the physics community in the UK as a whole, acting as a true national asset as a University-based national facility for physics. It will support the endeavours of all UK physics departments through collaborations, the provision of fellowships and other initiatives to make facilities in the Cavendish available to the wider physics community.

Organisms develop from a single fertilized egg by increasing the number of cells through cell division, making those cells different from each other and, most importantly, organizing them in space to give rise to tissues and organs. This organization requires the emergence of systems of spatial coordinates that guide the arrangement of the different cells. A well accepted view of the process contends that there are gradients of special proteins, called morphogens, that can instruct cells what to do in a concentration dependent manner. This means that in a developing group of cells, there is always some pattern of instructions that cells read and that acts as a template for the process. An alternative view is that there is no such template and cells self organize from an initial situation in which all cells are equivalent. Understanding this second possibility has been difficult for lack of an adequate experimental system. Recently we have used mouse Embryonic Stem cells to create a system that recapitulates the events that take place in the early mouse embryo. This system is robust and reproducible and, together with classical genetic analysis, provides a versatile experimental tool to study processes of pattern formation. Here we propose to use this system to explore the mechanisms that pattern the early mouse embryo. Specifically we focus on a protein called Nodal that genetic analysis has shown to be crucial for the early patterning of the mouse embryo. One of the challenges of modern biology is to integrate large amounts of data, particularly from gene expression, into coherent frameworks that account for specific processes e.g the development of an organ like the heart, or a tissue, like the skin. In this process the acquisition of quantitative data about the system and its integration into predictive models is a most important part of the research. In this project we propose to do exactly this by focusing on Nodal and following preliminary results that suggest that it acts as the key element in the process of pattern formation in the aggregates as it does in the embryo, though we do not understand the mechanism of the process that mediates the patterning. In the proposed experiments we shall engineer versions of Nodal and associated proteins that will allow us to follow the patterning process live, extract quantitative data about it and combine it with classical genetic analysis in a useful and fruitful manner. The experimental system will be our patterned aggregates that will allow us to bypass the embryo and explore the role that mechanical forces play in the pattern forming process and how it interferes with the better understood biochemical events.

This proposal focuses on understanding the complex biology of normal and mutant stem cells by linking single cell function with single cell molecular profiles. It will combine single cell functional and molecular assays with flow cytometric index-sorting and mathematical modelling in an iterative manner across both normal and mutant stem cell populations. This project requires partners with diverse expertise in single cell functional biology (Kent group), single cell molecular biology (Gottgens group) and computational modelling (GSK Systems Modeling and Translational Biology Group). Mathematical models will be developed by the industrial partner (GSK) to understand the scale and speed of clonal expansion in vivo and this will be compared to indexsorted single cell proliferation and differentiation data collected in vitro. These data will be integrated with single cell RNA-sequencing data of stem/progenitor cells generated for this project and also other projects in the Kent/Gottgens labs to provide a comprehensive molecular understanding of distinct fate choices in single stem cells. Overall this project has the following three objectives: Objective 1:To understand the extent of blood stem cell heterogeneity in vitro and how it relates to the distinct subtypes observed in single stem cell transplantations. Objective 2: To compare cellular dynamics observed in Objective 1 to mutant stem cells with increased (TET2 loss-of-function) or ecreased (JAK2 gain-of-function) self-renewal activity to determine which properties are associated with durable self-renewal. Objective 3:To determine regulators of stem cell self-renewal and functional heterogeneity at the protein level by index-sorting and tandem flow cytometry / mass spectrometry (CyToF).

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at www.rcuk.ac.uk/StudentshipTerminology. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.