Research projects available for BMedSci students for the year 2018-2019 are listed below. To narrow down your search by department or keywords, use the search box on the right-hand side.
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ANAESTHETICS: Electronic Pre-Operative Assessment Evaluation of the impact of ePAQ-PO on patient care
Please enter the aims and objectives of the project in the box below *
1) To understand patients’ personal experience & cost of pre-operative assessment for less fit & healthy (ASA grade 2 & 3) patients.
2) To evaluate compliance with electronic interviewing in terms of completion rates and completion times in this group of patients.
3) To evaluate patient flow through the pre-operative assessment pathway in users and non-users of ePAQ-PO.
Categorised under: STH/SCH
Diabetic foot ulceration is the commonest cause of hospitalisation in people with diabetes and also the commonest reason for lower limb amputation in the UK. Although there is now strong evidence regarding interventions to reduce ulceration and amputations, the incidence remains stubbornly high. The selected BMedSci student will be involved in carrying out a variety of studies as part of a major service review of the diabetes foot service in Sheffield and in Y&H. A key part of the project will be to try and determine factors that result in people with diabetes presenting with recurrent foot ulceration or progressing to amputation. Many also die prematurely. This is still a poorly understood area and better understanding of these factors could lead to the deployment of strategies to improve outcomes. This study will involve prospectively following up people who have presented with ulcers and determining what factors at baseline predict for how they are likely to progress. This is an ongoing study and the student will have access to a large database of cases collected by previous students. Another project will involve working within the Yorkshire and Humber Diabetes Clinical Network to help facilitate, analyse and present the results of a regional root cause analysis (RCA) of all major amputations
Categorised under: STH/SCH
Women with Pelvic organ prolapse undergoing surgery will have their voiding assessed before and after surgery to identify how voiding changes. We will analyse the Qmax and voiding dysfunction using the Liverpool Nomograms pre and postoperatively. We will also collect data on age, parity, menopausal status, stage of prolapse and underlying urinary incontinence. We will also analyse a cohort of patients who chose a ring pessary to see what impact this has on voiding compared to women undergoing surgery. Students will collect data on uroflowmetry before and after surgery and insertion of a ring pessary. They will plot this data on the nomogram and compare pre and postoperative data as well as comparing data with women choosing a ring pessary.
Categorised under: STH/SCH
In vitro studies to determine which major vaginal microfloral species contribute to the cervicovaginal fluid metabolite profiles observed in women destined to deliver preterm
To compare metabolite profiles from cervicovaginal epithelium produced by species that cause bacterial vaginosis (BV, associated with preterm birth), to those produced by commensal Lactobacillus species (which are protective against infection and preterm birth).
Categorised under: Oncology and Metabolism
Exploring the potential of augmenting kinesin mediated axonal transport as a therapeutic intervention in neurodegeneration.
Neurons form complex extended cellular structures. For example, motor neurons have cell bodies in the spinal cord whilst extending axons down to the muscles of the hands and feet. This presents a problem for neurons as the majority of newly synthesized protein is made in the cell body and then transported down the axon to its site of use, up to 1 meter away. Axonal transport is essential for maintaining axon integrity and defects are observed in many neurodegenerative conditions including Alzheimer’s, Parkinson’s, Huntington’s and ALS. Long distance transport in axons is carried out by microtubules and the motor proteins, dynein and kinesin. Due to the unique organisation of microtubules in the axon, kinesin motors are responsible for all anterograde transport from the cell body to the distal axon. Anterograde transport of different classes of cargo along the axon varies in velocity from 0.1 to 400 mm/day. Consequently, active axonal transport of new material takes place over periods of minutes to days, or even weeks and is subdivided into ‘fast’ and ‘slow’ transport classes. Critically, transport rates are determined by the time spent engaged with an active kinesin motor, rather than the speed of the motor itself. The majority of newly synthesised protein in the axon is moved by slow axonal transport, powered by transient interactions with kinesin. Understanding the molecular details of this transport process is crucial to providing new avenues for treatment in neurodegeneration. For some time, it was thought that kinesin motors are present in excess within cells, and that kinesin’s potent autoinhibition mechanism controlled recruitment to cargo. However, based on extensive experimental observations we recently proposed the ‘kinesin-limited’ model of slow axonal transport, stating that kinesin is in rate limiting supply for slow axonal transport cargos. One important consequence of this model is that overexpressing kinesin or augmenting its activity could increase the rate of slow axonal transport; this could provide downstream positive effects on protein homeostasis in the axon, making it a potential treatment avenue for diverse conditions linked to decreases in axonal transport. During this project, you will directly test the hypothesis of the kinesin-limited model. You will do this by first cloning vectors for the tandem expression of the kinesin holoenzyme with axonal transport reporters. You will then test the expression of these constructs in cell lines using transient transfection techniques, followed by western blotting and fluorescence imaging of fixed cells. Following successful test expression, you will assess changes in axonal transport caused by kinesin overexpression using live cell imaging of differentiated neuronal cell lines.
Categorised under: Department of Neuroscience
Rare genetic diseases often manifest as chronically debilitating, progressive illnesses that have a destructive impact on quality of life for affected individuals and their families. In many cases, these conditions also dramatically diminish life expectancy. Although these diseases are individually rare, the term ‘rare disease’ has been ascribed to over 6,000 distinct medical conditions. These are collectively estimated to affect around 30 million people in the EU alone, thus posing a tremendous burden to society. It is now increasingly feasible to identify the genetic defects underlying rare disease, and by studying these genes we can hope to gain insight into complex biological pathways underpinning human health and disease. We are particularly interested in rare neurodevelopmental or neurodegenerative diseases. In this project you will investigate a group of related rare diseases caused by mutations in genes that all function in a single biochemical pathway, and yet have distinct effects on the cerebellum, and thus distinct clinical phenotypes. It is only by modelling these disorders in a vertebrate system that we can determine how these mutations give different cerebellar phenotypes, and hence gain insight into the role of this pathway in the cerebellum. Aims of the Project: (1) Use genome editing to introduce novel pathogenic human mutations into the orthologous zebrafish genes. (2) Characterisation of mutant zebrafish that have already been developed bearing mutations in genes in this pathway. (3) Analysis of the impact of these mutations on cerebellar development and degeneration in zebrafish.
Categorised under: Department of Neuroscience
Setting the body’s threshold of sensitivity to stress: elucidating the roles of cytoplasmic tethering factors in regulating the Glucocorticoid Receptor in health and disease.
Chronic exposure to persistent biological stressors in the physical or social environment can threaten wellbeing and increase risks of mental ill-health. In humans, the glucocorticoid cortisol is the main hormone responsible for co-ordinating physiological responses to stress. Cortisol acts primarily as a ligand for the Glucocortocoid Receptor (GR), which modulates transcription of its target genes in response to changing levels of cortisol. GR is normally sequestered in the cytoplasm as part of a complex involving the proteins FKBP5 and HSP90, but dissociates from these proteins after cortisol binds to GR, enabling its translocation to the nucleus and modulation of target gene transcription. Interestingly, cortisol-bound GR promotes transcription of the gene encoding FKBP5. Moreover, genetic and epigenetic changes that alter levels of FKBP5 transcription are associated with psychiatric disorders and poor mental health (Zannas et al., 2016, Neuropsychopharmacology Reviews 41:261-274). We hypothesise that FKBP5 and HSP90 act as parts of a cytoplasmic tethering complex for GR, which sets the threshold concentration of cortisol required to promote GR translocation to the nucleus and generate GR-mediated stress responses. We further hypothesise that altered levels of FKBP5 and HSP90 expression or activity can increase or decrease the sensitivity of target tissues, such as the brain, to cortisol, thereby altering levels of GR target gene transcription. These changes may affect brain development and function, and in people exposed to chronically high levels of stress, contribute to their poor mental health. Aim: The main aim of this project is to test the hypothesis that altering the levels of FKBP5 and/or HSP90 activity, using specific pharmacological manipulations, alters the sensitivity of the GR and its target genes, to biological stressors. We will employ the pharmacologically and genetically tractable zebrafish as an experimental model organism in which to test this hypothesis. The supervisors (Dr Vincent Cunliffe and Dr Nils Krone) have extensive experience of research with zebrafish to elucidate the molecular and cellular mechanisms underlying disorders of the endocrine and central nervous systems, both independently and collaboratively. Objectives: 1. Investigate the effects of exposing wild-type zebrafish larvae to the FKBP5 and HSP90 small molecule inhibitors, on phenotypes such as larval behaviour and GR-dependent target gene expression. 2. Determine the roles of GR and cortisol downstream of the effects of exposure to FKBP5 and HSP90 inhibitors on behaviour and gene expression, by comparing the phenotypes of wild-type zebrafish larvae and larvae with mutations in the gene encoding GR, or other genes required for cortisol biosynthesis. 3. Evaluate the impacts of exposing wild-type and mutant larval zebrafish to FKBP5 and HSP90 inhibitors, by comparing their behavioural and transcriptional responses to physiological stressors and cortisol analogues such as beta-methasone. References: Eachus H, Zaucker A, Oakes JA, Griffin A, Weger M, Güran T, Taylor A, Harris A, Greenfield A, Quanson JL, Storbeck KH, Cunliffe VT, Müller F, Krone N. Genetic disruption of 21-hydroxylase in zebrafish causes interrenal hyperplasia. Endocrinology. 2017 Sep 13. doi: 10.1210/en.2017-00549. [Epub ahead of print] Eachus H, Bright C, Cunliffe VT, Placzek M, Wood JD, Watt PJ. Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function. Hum Mol Genet. 2017 Jun 1;26(11):1992-2005 Cunliffe VT. The epigenetic impacts of social stress: how does social adversity become biologically embedded? Epigenomics. 2016 Dec;8(12):1653-1669 Griffin A, Parajes S, Weger M, Zaucker A, Taylor AE, O'Neil DM, Müller F, Krone N. Ferredoxin 1b (Fdx1b) Is the Essential Mitochondrial Redox Partner for Cortisol Biosynthesis in Zebrafish. Endocrinology. 2016 Mar;157(3):1122-34. doi: 10.1210/en.2015-1480.
Categorised under: Department of Biomedical Science