In order for an animal to survive, its individual cells must be able to communicate with each other and respond appropriately to external factors such as changes in their environment or infection. The main way in which a cell achieves this is through the activation of intracellular signalling networks. These have many roles, but one important aspect of their function is regulating which genes are active in the cell, since changes in gene regulation are important in mediating many of the long-term effects of signalling. Deregulation of signalling networks and gene regulation frequently has adverse effects and occurs in many diseases, including cancer, neurodegeneration and inflammatory diseases such as arthritis and asthma. Compounds that selectively target these mechanisms therefore have great potential to treat these diseases. Indeed some have already been approved for use or are in clinical trials. Despite advances in this area, much is still not understood about the regulation of normal and pathological function, of the various signalling cascades in cells. Our work is focused on the functions of mitogen activated protein kinase signalling cascades, one of the signalling cascades implicated in cancer and inflammatory disease. In particular we are interested in understanding how they regulate the transcription of specific genes and how this in turn affects the function of cells in neuronal and immune systems.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

The primary aim of this project is to develop a simulation of the processes involved in solving the following problem: how to select, based on the agent's knowledge and representations of the world, one object from several, grasp the object and use it in an appropriate manner. This mundane activity in fact requires the simultaneous solution of several deep problems at various levels. The agent's visual system must represent potential target objects, the target must be selected based on task instructions or the agent's knowledge of the functions of the represented objects, and the hand (in this case) must be moved to the target and shaped so as to grip it in a manner appropriate for its use. We propose to develop a robotic simulation model inspired by recent theories of embodied cognition, in which the vision, action and semantic systems are linked together, in a dynamic and mutually interactive manner, within a connectionist architecture. Human experimental work will constrain the temporal and dynamic properties of the system in an effort to develop a psychologically plausible model of embodied selection for action. As much of the cognitive mechanisms leading to the integration between action and vision for actions such as object assembly tasks are not fully known, new empirical studies in this project will also improve our insight of these embodied cognitive dynamics. New experiments and the use of the embodied cognitive model will also be used to further our understanding of language and cognition integration e.g. by providing further predictions and insights on the dynamics of language and action knowledge in object representation.This is an interdisciplinary project which involves expertise and methodologies from cognitive psychology, motor control, and computational/robotics modelling. The interdisciplinary nature of the project and the design and experimentation of cognitive agents make the project highly relevant to the Cognitive Systems Foresight programmeBehavioural studies, as proposed here, will be based on the eye-tracking methodology. This permits the identification of the time-course of visuo-attentional processes in action and language processing and will provide converging evidence from stimulus-response compatibility studies on object selection. Eye tracking data will also be used to constrain the behavioural and attentional strategies used by simulated cognitive robots during tasks involving object naming and selection. In eye-tracking experiments we will show arrays of novel objects and study three levels of action representation. At the encoding level, we manipulate the location and onset time of a visual detection probe in this array to reveal how observers attend and prepare their actions (Fischer et al., in press). At the representational/linguistic level, we present auditory object names and register the observer's eye movements towards the named objects (visual world paradigm, e.g. Altmann & Kamide, 2004). Linguistic manipulations, such as using phonological competitors ( candle-candy ), reveal the time course of the interplay between covert and overt attention and the relative strength of top-down (linguistic) vs bottom-up visual control over action prediction. Finally, at the execution level, we instruct participants to pick up the named object and record their overt manual responses (e.g., Chambers et al., 2002, 2004). Orthogonal to these three levels of embodiment, we gradually associate each novel object with a particular name and manual response, and we design object arrays with congruent and incongruent response requirements. This learning approach enables us to track embodied concept acquisition and its implications for action control, separately at the encoding, linguistic/representational, and execution level.

The majority of plant genes contain intervening sequences (introns). When a gene is turned on (transcribed), the DNA code is copied into a molecule of RNA called precursor messenger RNA (pre-mRNA). Intron sequences are removed from pre-mRNA by the process of splicing which joins the coding regions of genes (exons) together. The spliced mRNA is then translated into a protein. In many cases, in both plants and animals, pre-mRNAs can be spliced in different ways to generate different mRNAs / this is termed alternative splicing (AS). The alternative mRNAs produced can encode different proteins with different functions such that, for example, in humans, the 35,000 genes in the genome can give rise to more than 150,000 proteins. Thus, AS modulates gene function and expression and increases the number of proteins in higher eukaryotes. This flexibility allows the cells in an organism to fine-tune and subtly regulate cell activity. AS is not a random process but is highly regulated through the interaction of a large number of proteins called splicing factors with sequence signals in the pre-mRNA. Thus, in a particular cell type, the profile of splicing factors will determine the pattern of alternatively spliced transcripts of all of the genes being expressed. This will differ in different cell types, at different stages of development and in response to stimuli and, for example, stress conditions. To understand the regulation of gene expression at the level of alternative splicing, it is necessary to be able to measure changes in alternative splicing of multiple genes under different conditions. Over the last five years, estimates of the number of plant genes which undergo alternative splicing have risen from 7 to 35%. Despite at least a third of plant genes being alternatively spliced, little is known about how alternative splicing is regulated in plants. In particular, there is a need to better assess AS and its consequences, to address the co-ordinated regulation of AS in genes involved in the same biological process and to be able to examine cell- and tissue-specific alternative splicing. One of the major drawbacks currently is the lack of an accurate and reproducible system capable of monitoring multiple (10s to 100s) of AS events simultaneously. Research in animal systems has shown that alternative splicing is an essential aspect of gene expression with networks of alternative splicing regulation being superimposed on networks of transcriptional regulation. In plant systems, measuring global transcript levels is carried out routinely (transcriptomics) but alternative splicing and, in particular, the concept of co-ordinated and regulated alternative splicing has been largely ignored. We wish to establish a tool to monitor changes in alternative splicing of multiple plant genes in development and stress responses. The project will build collaborations between groups involved in aspects of developmental and stress biology of plants and the RNA biology/alternative splicing lab at the University of Dundee. The outcome of the project will be the demonstration that comprehensive process-specific AS RT-PCR panels can be used to accurately analyse changes in alternative splicing during development, under different conditions and in different mutant lines. By correlating patterns of changes in alternative splicing of specific genes or subsets of genes, information on the co-ordinated regulation of AS will be produced for the first time. Such information will be an integral part of systems approaches aimed at understanding interaction networks which regulate biological processes. The tool which we will develop will be of interest to plant scientists around the world. Although we will establish the tool by studying developmental processes and stress-induced genes in Arabidopsis, the system is very flexible and can be applied to examine any biological process in any plant species for which reasonable EST data exists.

The goal of 3Dface@Home is to develop and test a system to robustly obtain highly accurate facial 3D reconstruction from end users' mobile devices in real world conditions, such as one's smartphone at home. It is made of a mobile application allowing the user to capture images of their face by themselves with guidance and validity check. Those images are sent to a computational server where a deep learning based facial 3D reconstruction embedding multi-view geometry constraints will be used to obtain the 3D shape of the face. The project will aim to reach sub-millimetre accuracy required for measuring anatomical structures in the context of disease affecting facial growth. A purpose-built dataset will be acquired, including examples of facial dysmorphology, and reflecting real world conditions the system needs to be robust to such as bad illumination, blurry images or partial occlusion. In the future, this work will facilitate mass collection of data for genetic studies on disease affecting facial growth and enable the exploration of clinical translation in a variety of medical fields.