- Total grants
- Total funders
- Total recipients
- Earliest award date
- 20 Nov 1998
- Latest award date
- 31 Mar 2020
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Student electives for Justine Downing, Jennifer Muir, Michelle Perera and Wendy Thomson. 19 Jul 2006
Historical and conceptual links between Pierre Janet and Eugen Bleuler's (1911) concept of schizophrenia: A preliminary exploration. 26 Apr 2006
Historical and conceptual links between Pierre Janet and Eugen Bleuler's (1911) concept of schizophrenia: A preliminary exploration In the broadest terms, this project aims to explore the historical and conceptual roots of Eugen Bleuler's concept of schizophrenia, and its impact in Britain. The basic hypothesis is that the influence of Sigmund Freud on Bleuler's thinking has been overrated (including by Bleuler himself), with a corresponding devaluation of the extent to which Bleuler was influenced by Pierre Janet and his concepts, along with allied 'dissociationists' (such as Theodore Flournoy). The research attempts to trace the development not only of Bleuler's concept of schizophrenia, but also of the fundamental terms 'loosening' ('Lockerung') of associations, 'splitting' ('Spaltung') and complexes ('Komplex'). I am also seeking to trace Bleuler's contact with a variety of figures, and trace the significance of their influence on him, including Charcot, Forel, Wundt, Wernicke, Breuer, and, of course, Freud. Perhaps the most important is the influence of Carl Jung, Bleuler's colleague at the Burgholzi Hospital during the crucial years the concept of schizophrenia was being developed, and his 'second in command' for many years. The questions to address are: 1) When did Bleuler first formulate his ideas on 'loosening' of associations, and what influenced him in this regard? 2) Did Bleuler ever meet Janet? Did he have any direct contact with him? 3) How important an influence was Breuer and Freud's 'Preliminary Communication' in 1893 on Bleuler's developing ideas? 4) How much of an influence did Jung's ideas, particularly his 1907 book on Dementia Praecox have on Bleuler? 5) Why was Bleuler so enthusiastic about Freud? 6) How affected was Bleuler and the other Burgholzi physicians by Jung's sojourn with Janet in 1902-1903? 7) When was the term 'schizophrenia' first used around Burgholzi? 8) After Bleuler's book was published in 1911, did Freud read it? 9) Is there any historical record around Manfred Bleuler's invitation to Pierre Janet in 1946 to come to Zurich? Did he feel that Janet was an important influence on his father?
Common symptoms in the community: understanding the public's responses to inform the development of interventions. 13 Dec 2005
Recent UK government policy has advocated more extensive use of primary care teams, including nurses and pharmacists, for the management of common ailments, as well as promoting self-care of symptoms indicative of self-limiting illness. We do not currently know how the public is responding to these strategies or what influences their own management decisions. The aim of this research is to determine patterns of common symptoms in the community, and understand how the public responds to them, in order to enhance appropriate and effective management of common symptoms. The first phase of the research will be a population-based postal survey which will determine the patterns of common symptoms in the community, identify how people currently manage their symptoms, and identify factors associated with different patterns of management. The second phase will be a discrete choice experiment which will investigate the relative importance of different factors influencing management decisions and the trade-offs people make when deciding how to manage their symptoms. The final phase will be a literature review of primary care-based interventions previously used to manage common symptoms. The work will lead to the development of interventions to be used in primary care to optimise appropriate health care.
Biomphalaria glabrata: gene discovery, expression, profiling and interval mapping to elucidate mechanisms of resistance to Schistosoma mansoni. 14 Dec 2005
To promote an understanding of snail-schistosome interactions and development of novel intermediate host-based control strategies an EST gene discovery approach is proposed, to increase significantly the genomic database of B. glabrata, the intermediate host of Schistosoma mansoni, a major schistosome infecting man. There is international interest to commence genome sequencing of this important mollusc, and parasite resistance is the trait currently perceived as the most crucial. Isolation of transcripts by gene discovery approaches, and identification of those involved in resistance, by microarray analyses, will create the initial impetus for a genomic analysis of B. glabrata. Quantative trait loci (QTLs) will be identified through interval mapping, using preliminary linkage maps, incorporating genome-wide markers, using populations segregating for schistosome resistance. Combining microarrays with mapping will accurately identify candidates conferring resistance, separating causal from secondarily effected differentially expressed genes. The map position of each transcript will be improved progressively, and genes differentially expressed between resistant and susceptible snails and lying within a QTL will be further characterized. This work will provide the initial impetus for further genomic characterization of B. glabrata, allowing for future integration of parasite and intermediate host genomics to elucidate their co-evolution and suggest novel interventions.
Understanding how to stimulate and direct nerve regeneration is crucial. Using rat cornea, we showed for the first time that the cues directing nerve growth and wound healing in vivo include wound-generated electrical signals (Song et al, 2002, 2004 & front cover). These signals arise the instant the wound occurs and remain until the wound closes. Direct current electrical fields (DC EF) of the same magnitude stimulate and direct nerve growth and wound healing in vitro (McCaig et al, 2002, 2005). Moreover, in a recent Phase 1 clinical trial to treat spinal cord injuries, patients implanted with long-term electrical stimulators showed return of significant sensory functions and of some motor activity (Shapiro et al, 2005). Nevertheless there is still only limited understanding and acceptance of electrical regulation of nerve guidance and wound healing. Therefore we propose two definitive tests. Using a unique combination of cell biology, biophysics, pharmacology and molecular genetics, we shall apply a DC EF directly to rat corneal wounds in vivo. If wound-directed nerve growth and wound healing are regulated electrically, the polarity and magnitude of the applied EF will determine whether these cell behaviours are enhanced or inhibited. In addition, we shall test the role of the EF in vivo using pharmacological and genetic methods of disrupting the electrical seals formed by the epithelial tight junctions.
The University of Aberdeen seeks funding To carry out a professional conservation survey of its extensive early medical archives and To purchase custom archival folders and boxes for their immediate re-housing. In June 2005, the University was notified of a successful application to the Wellcome Trust's Research Resources in Medical History scheme to catalogue its early medical archives, dating from the 15th century to 1860. The 100 collections submitted for cataloguing include medical lecture notes, treatises, prescriptions, herbals, patients' case notes, dispensary records, records of medical societies and individuals, including correspondence, diaries and journals. In terms of their physical extent, this amounts to 200 volumes and 20 boxes of papers. Cataloguing is scheduled to begin in May 2006. In advance of the cataloguing, it is proposed that staff from the highly respected University of Dundee Book & Paper Conservation Studio carry out a conservation survey on all the project collections and produce a condition report. The condition report will include treatment proposals and costings, as well as recommendations on storage, housing, and environmental conditions. Re-housing of these collections is additional and complementary to the conservation survey, and will not commence until the condition report has been received. Funds are not being sought in this bid to cover the costs of active conservation repair: where this is recommended, additional funds will be sourced at a later stage.
We have established that bacterial cells require cellular homeostasis for growth and survival in diverse niches. Ion channels play major roles in cellular homeostasis, as exemplified by our previous work on mechanogated (MscS & MscK) and electrophile activated (KefC) channels. We have made considerable progress in understanding the gating of these two channel types and the future programme will concentrate specifically on the gating transitions in the channels. Additionally, we will pursue high resolution structures for the closed state of both MscS and MscK and assess important regions of the KefC structure in order to link them to function. The team members have become expert in electrophysiology, molecular genetics and protein biochemistry and they have made significant contributions to understanding the mechanisms and physiological roles of bacterial ion channels. The programme builds on these core skills, which will be augmented by strategic structural and biophysical collaborations (Naismith & Perozo). The key objectives will be:(a) Detailed understanding of the gating transitionof the MscS and MscK channels.(b) Closed structures for MscS and MscK.(c) Structural analysis of KefC - definition of the ion translocation pathway and the gating transition.
The central hypothesis underpinning this programme is that the molecular architecture of the Candida albicans cell surface strongly influences virulence, immune recognition and disease causation by this major fungal pathogen of humans. In a previous programme grant we showed that cell wall glycosylation and other specific cell wall components are essential for the growth, virulence and the immune response to C. albicans. Also, we generated a comprehensive set of molecular tools and reagents to study the relationship between the cell surface and C. albicans pathogenesis. We will now establish how specific cell surface components influence pathogen recognition and disease, and how these components are regulated during growth, responses to environmental stresses and host invasion. We have four specific objectives: (1) to undertake a detailed functional analysis of O- and N-mannan assembly as a route to investigating the importance of these surface polymers in pathogenesis; (2) to understand the effects of altering surface mannoproteins upon virulence; (3) to determine the role of cell wall surface components in stimulating the innate immune response, and (4) to define the molecular plasticity of the cell surface in relation to changing microenvironments in vitro and in vivo.
Personality disorder and moral responsibility. 28 Mar 2006
When psychiatrists address the issue of personality disorders, they do so from two standpoints. On the one hand, they try to place these in an explanatory, deterministic context. On the other, they often face the task of deciding when and to what extent patients with personality disorders should be held responsible for their actions. Moral responsibility rests on assumption of free will i.e. that the person could have done otherwise. However, some of history's famous moral statements (e.g. Martin Luther, "Here I stand, I can do no other") make it clear that the freedom or otherwise of actions may not be the critical issue. Instead, we may need to focus on moral character and the extent to which an individual is responsible for this. Theories of free will exist on a spectrum which runs from "hard determinism" at one end, through various "compatibilist" theories (i.e. that free will is compatible with determinism or that moral responsibility is compatible with the absence of libertarian free will) to "radical libertarianism" at the other (Kane, 2002). Determinist theories of action have a clear plausibility but also pose a serious threat to any concept of a moral order and to many of our ideas of what confers value on persons. The present project has two main aims. The first of these is to review recent thinking on free will and to apply this to the issue of personality disorder and moral responsibility. The second is to examine ways in which we might be seen as responsible for our moral characters. This will seek to extend my work on the psychology of aesthetics.
The aim of this project is to develop a protocol whereby human embryonic stem cells (hESCs) can be induced to differentiate into insulin secreting Beta cells. The hESCs will be cultured in chemically defined media in the presence of growth factors that promote differentiation of endoderm. We will also generate hESC lines that have been stably transfected with DNA constructs in which fluorescent reporter proteins are expressed under the control of regulatory sequences of genes encoding transcrip tion factors that control beta cell differentiation. These lines will be used to optimise culture conditions for the differentiation of endoderm-enriched hESCs towards Beta cells. To assure differentiation towards a Beta cell like phenotype we propose to induce expression of transcription factors that are known to control islet development. We have constructed a novel plasmid in which a superactive form of the transcription factor PDX1, i.e. PDX1VP16 is fused to a 4 OH-tamoxifen responsive seq uence, ERT2. The plasmid is configured such a way that it should be possible to replace the PDX1 coding sequences with sequences for PAX4, BETA2, ngn3 or other factors that are known to control islet cell differentiation. The hESC-derived Beta cells will be characterised in vitro and in mouse diabetic models.
Effects of in-utero exposure to environmental chemicals via maternal pasture ingestion on fetal development. 11 Jul 2006
Current understanding of possible detrimental effects of exposure to environmental chemicals (ECs) on fetal reproductive development relies on toxicological studies of short-lived rodents exposed to high doses of single/small numbers of compounds. We will employ a long-lived species, the sheep, to investigate effects on fetal development of a real-life , chronic, low-level exposure of ewes to a relevant cocktail of ECs, including endocrine disrupting compounds (EDCs and heavy metals. Ewes will be maintained on pastures fertilised with either inorganic fertiliser (Control) or sewage sludge (EC cocktail). Maternal and fetal EC levels will be measured and related to endocrine systems and hypothalamo-pituitary and gonadal development and function at 55 & 110 days of gestation, and in adult offspring. Specific effects of fetal exposure via continuing maternal intake of ECs will be distinguished from those solely due to mobilisation of maternal EC loads. This will be done by switching Contr ol ewes to sewage sludge-fertilised pastures, and vice versa, immediately prior to mating, with slaughter at 110 days of gestation and measurements as above. Our key goals are to determine the extent to which EC exposure (1) disrupts fetal development, (2) compromises adult reproductive function and (3) relies on mobilization of maternal EC loads.
In June 2005, the University of Aberdeen was notified of a successful application to the Wellcome Trust's Research Resources in Medical History scheme to catalogue its early medical archives, dating from the 15th century to 1860. These unique records include medical lecture notes, treatises, prescriptions, herbals, patients' case notes, dispensary records, records of medical societies and individuals, including correspondence, diaries and journals. In all, some 100 collections, comprising some 200 volumes and 20 boxes of papers, will be listed in detail and the subsequent catalogue made available for the public to search via the Internet. Cataloguing began in May 2006. A subsequent Wellcome-funded conservation survey was carried out on these collections, and as a result of the report recommendations, the University of Aberdeen now seeks funding to employ a paper/book conservator for one year to carry out the recommendations of the survey. The Project Conservator would carry out the work in-house, with cleaning and treatment carried out in the internationally respected conservation laboratory of the University's Marischal Museum, before re-housing the volumes in custom-made archive boxes or conservation grade folders as appropriate. The Project Conservator would work in close consultation with the Project Archivist and the Project Manager to develop a programme of cleaning and repair that complemented and supported the cataloguing activity. It will take one year to carry out the treatment proposals recommended in the report.
Neurodegenerative diseases pose one of the largest challenges in both the clinical and the research setting. My group has investigated the fundamental mechanisms underpinning cell death in Parkinson's disease (PD), which originates from the loss of dopaminergic neurons. We have demonstrated that cyclooxygenase (COX)-2 expression is increased in dopaminergic neurons in the substantia nigra pars compacta of PD patients (Teismann et al., PNAS 2003). In our Parkinson's disease model, mice treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), equivalent observations were made. COX-2 is instrumental in MPTP-induced neurotoxicity but our data suggest that the mechanism is not mediated by inflammatory cells (microglia/astrocytes). Our data are consistent with a major role for prostaglandin (PG) E2. Thus, COX-2 activity is paralleled by an increased expression of PGE2 in dopaminergic neurones. PGE2 can induce cytokine release and deprive the cell of oxygen, thus leading to cell death. In the proposed project we will investigate the function and mechanisms of PGE2 in the
Predictive genomic and transgenic analysis of tachykinin gene regulatory systems in the amygdala. 12 Oct 2006
The products of the TAC1 gene, that include the tachykinin substance-P, are expressed in the amygdala where they play an important role in the modulation of fear and anxiety. Understanding the systems that regulate TAC1 expression in the amygdala may provide an important step towards understanding the causes of chronic depression and anxiety that affect 10% of the UK population at some point in their lives. We have used a novel series of post-genomic bioinformatic strategies in combination with transgenic analysis, immunohistochemistry and transgenic organotypic culture to provide evidence that a remote amygdala specific enhancer drives the expression of TAC1 in the amygdala under the influence of the MEIS-1 transcription factor. We will use our unique transgenic lines, that express a marker gene under the influence of ECR1, and the combined skills of all four applicants to examine 1. the DNA-protein interactions, 2. the signal transduction pathways and 3. the ligand receptor interacti ons that make up the regulatory systems that modulate ECR1 activity in the amygdala in both unstressed and mildly stressed transgenic models. Understanding how these regulatory systems operate will facilitate the identification of novel drug targets and the development of more efficacious and specific anti-depressive and anxiolytic therapies.
In-vivo and In-vitro Control of Adult Neural Progenitor Differentiation in the Hippocampus by Retinoic Acid. 06 Feb 2007
All-trans retinoic acid (tRA) has been widely investigated as a regulator of the embryonic CNS , a topic we have extensively studied [2-10]. Much less is known however regarding its influence on the adult brain . We were the first to show that RA influences one aspect of hippocampal neuroplasticity neurogenesis [12, 13] and this proposal tests a new hypothesis that a precise equilibrium of tRA is essential to maintain this process. We will test this hypothesis by disrupting the bal ance of RA either by over-stimulation via treatment with 13-cis RA, used in the anti-acne drug Accutane  or under-stimulation using a retinol-binding protein null mutant mouse as a model for vitamin A deficiency. The effects of imbalance will be tested on three defined, quantifiable aspects of neurogenesis, determining: 1) the influence of varying RA concentrations on neuronal birth, 2) candidate cell cycle proteins influenced by RA and 3) RA s influence on neuronal maturation. New modulat ors of neurogenesis are currently sought because of their potential importance in CNS repair and psychiatric disease [15-17] and this proposal will characterize a new neurogenic modulator unique because of its ability to be adjusted by both dietary and genetic means.
Diet and autoimmunity: modulation of the myelin oligodendrocyte glycoprotein specific T cell repertoire by the milk protein butyrophilin. 08 Feb 2007
Sensitisation to the milk protein butyrophilin1A1 (BTN) initiates an immune response that cross-reacts with myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in multiple sclerosis (MS). This cross reactivity can be exploited to expand regulatory T cell populations that suppress the encephalitogenic potential of MOG-specific T cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This project will exploit the availability of BTN deficient C57 BL/6 mice to test the hypothesis that epitopes derived from autologous BTN play a major role in shaping the composition/function of the endogenous MOG-reactive autoimmune T cell repertoire. Specifically, we will investigate: (1) The mechanism(s) by which immunological self-tolerance to autologous BTN is established. (2) How epitopes derived from autologous BTN influence the composition/function of the MOG-reactive T cell repertoire and susceptibility to MOG-induced EAE. (3) How sens itisation to autologous BTN may be exploited to suppress MOG-mediated autoaggression in adults.
Regulation of vascular smooth muscle cell phenotype by changes in phospholipase C gamma expression: relationship to the pathogenesis of vascular disease. . 22 Feb 2007
The molecular mechanisms regulating vascular smooth muscle (VSM) cell proliferation during vascular disease are not well understood. These mechanisms regulate selective gene expression leading to changes in protein expression necessary for proliferation. A previous study, and further preliminary evidence, has indicated that phospholipase C gamma (PLCg) expression is regulated dependent upon VSM phenotype both in vitro and in vivo. This study will examine the hypothesis that these changes in PL Cg expression can act as a molecular switch and regulate VSM phenotype towards either proliferation or differentiation. It is proposed that this mechanism occurs via the selective activation of the Ca2+-dependent phosphatase, calcineurin and subsequent regulation of key transcription factors. Experiments will use overexpression/knockdown of PLCg in cultured VSM cells to determine how changes in growth factor-stimulated pathways correlate with altered PLCg expression. These pathways will inc lude Ca2+ signalling, transcription factor activation/interaction and ultimately regulation of gene expression and growth. Further experiments will test the validity of this hypothesis using an in vivo vascular injury model. This study will uncover an important mechanism in regulating VSM phenotype and will further demonstrate that this may be involved in the development of vascular disease.
Directional cell migration plays an important role in development, wound healing and inflammation. There are endogenous wound electric fields and many types of cells, including human cells respond to an electric signal by directional migration (electrotaxis/galvanotaxis). We have pioneered in using a genetic tractable model organism--Dictyostelium discoideum to elucidate the molecular genetics of electrotaxis (Zhao et al., 2002). Based on a successful initial collaboration supported by the Trust , we have developed novel screen strategy and propose to identify molecules and genes important in sensing and responding to an electric signal. We will study systemically the role in electrotaxis of known molecules. This will focus on the molecules critical in chemotaxis, for example: heterotrimeric G-proteins; PI3 kinase / Pten; MAP kinase; small GTPases Ras. This will demonstrate some key sensing and signalling elements sharing or different between chemotaxis and electrotaix. We will in vestigate the role of membrane potential, extracellular ions and ion transportation in electrotaxis. Using our recently developed effective screening strategy, we will isolate strains with defects in electrotaxis from REMI mutagenised and chemically mutagenized cells. This will systemically screen for mutants and identify novel molecule and genes underlying electrotaxis.