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School of Biological Sciences - MRes Science Projects 2017/18 The Master of Research (MRes) Science course is a postgraduate course that will provide applicants with an opportunity to focus their research interests on one or two areas of science whilst also giving them the opportunity to work towards being able to translate their learning into research related outputs (e.g. submission for a peer-reviewed publication, peer reviewed research / knowledge transfer grant application, presentations). The MRes Science can be studied either full time (one year) or part time (two years) and will enable students to develop a wide variety of skills, experience, and competence throughout their studies. The MRes will provide a thorough grounding should students consider moving towards Doctoral (PhD) studies, or pursue research related activities as a career. Further information can be obtained at http://www.port.ac.uk/courses/mres-science The course is taught within the Faculty of Science and within the School of Biological Sciences. The projects for the September 2017 or January 2018 intake are shown below: Project Title: Structure of the 30 nm Chromatin Fibre. Supervisor: Dr Chris Read & Fiona Myers (with Prof. Colyn Crane-Robinson). Project Brief: Extracted native chromatin appears as a helical fibre of ~30 nm diameter but the internal arrangement of nucleosomes and DNA linkers between them is unknown. The project aims to determine this next level of compaction, the arrangement of nucleosomes in the fibre, by assessing nucleosome proximities, i.e. by defining adjacent, near and far neighbours, in a fully defined ‘bespoke’ 30 nm fibre. Within the fibre a pair of nucleosomes each bearing a fluorophore will report on their relative positions using FRET. A set of experimentally determined inter-nucleosomal distances can then distinguish between various models of the fibre. The project will build on the technologies we have established for constructing long nucleosomal arrays and for attaching fluorophore-containing nucleosomes using magnetic bead purification protocols. The student will make extensive use of recombinant, molecular biological and biophysical techniques, in particular fluorescence/FRET, electron microscopy (including AFM) and analytical centrifugation. Project Title: How Antifreeze Proteins Work. Supervisor: Dr Chris Read & Fiona Myers (with Prof. Colyn Crane-Robinson). Project Brief: Antifreeze proteins (AFPs) enable various organisms, e.g. Antarctic fish, to survive in freezing habitats by preventing the macroscopic growth of ice crystals within their bodies and cells. A general consensus has built up that regular structures on the surface of AFP proteins have the same repeat as water in ice and this can sequester any developing ice crystals. The presence of ‘ice-like’ water molecules on the surface of a protein should manifest itself in a very large enthalpy and entropy when the protein denatures. The aim will be to directly measure, for the first time, the heat (enthalpy) of AFP protein melting by differential scanning nano-calorimetry (DSC), to obtain the thermodynamic data for the ‘icelike’ water molecules. Project Title: Testing potential inhibitors for Dengue and Zika virus Supervisor: Simon Kolstoe / Andy Pickford Project Brief: Dengue fever is a mosquito born virus common in more than one hundred tropical countries. Each year up to 500 million people are infected leading to 20,000 deaths. The symptoms are similar to the common cold and gastroenteritis although there are higher rates of complications. The Zika virus is a related Flavivirus, and although it was first identified in 1947, has recently come to prominence due to an outbreak in South and Central America. The symptoms of Zika are similar to Dengue, although there are fears that Zika infection in pregnant women can also cause abnormal brain development in the unborn foetus (microcephaly). This project will focus on using a mammalian protein expression system (HEK293) to produce envelope protein for use in drug binding studies including NMR and X-ray crystallography. The project would suit a biochemistry graduate interested in drug development and/or protein structure-function relationships. Project Title: Probing drug mechanisms: serum amyloid p component Supervisor: Simon Kolstoe Project Brief: Serum amyloid p component (SAP) is a 125 kDa, pentameric, highly conserved human serum glyco-protein that circulates in all individuals at a concentration of 20-30 mg/l. SAP also makes up 14% w/w of amyloid deposits found in diseases such as the systemic amyloidosis, Creutzfeldt-Jakob disease, Alzheimer’s and type II diabetes. Small molecules that deplete SAP are currently undergoing clinical trials for the treatment of a number of amyloid related disorders. This project will use a variety of structural and molecular biology techniques (including cloning into human embryonic kidney cells and Xray crystallography) to elucidate the molecular details of SAP binding to a variety of physiologically relevant ligands. The student will gain experience in a number of techniques that are relevant to both academic and industrial research. Project Title: Using atomic force microscopy to study protein-fibril interactions Supervisor: Simon Kolstoe / James Smith (Pharmacy) Project Brief: Atomic Force Microscopy (AFM) is a technique that uses a micrometre-sized cantilever to probe surfaces and produce images at nanometre resolution, higher than that possible using light or electron microscopes. We have recently used this technique to gain preliminary images of aggregated insulin “amyloid” fibres. Amyloid fibres are found in a wide range of diseases such as the systemic amyloidosis, Creutzfeldt Jakob disease, Alzheimer’s and type II diabetes. This project will look at how amyloid fibres interact with a variety of accessory molecules found in pathological amyloid deposits; including glycosaminoglycans and the protein serum amyloid p component. Similarities between amyloid fibres and DNA will also be examined to explore how some molecules that normally recognize DNA also bind to amyloid. The student will gain experience in using AFM, creating and handling amyloid fibres in the laboratory, and exploring human fibres obtained through biopsies conducted by a collaborator. Project Title: Probing drug mechanisms: Transthyretin Supervisor: Simon Kolstoe Project Brief: Wild type transthyretin, the normal plasma protein that transports thyroid hormone and retinol binding protein, is inherently amyloidogenic and forms microscopic amyloid deposits of uncertain clinical significance in all individuals aged over 80 years. Massive deposits in the heart can also occur causing fatal senile cardiac transthyretin amyloidosis. We have previously developed a new method for targeted depletion of pathogenic plasma proteins (including transthyretin) using palindromic small molecule ligands. This project will build on previous drug discovery work by using biophysical techniques including isothermal titration calorimetry, small angle X-ray scattering and circular dichroism to further probe drug-protein interactions. The student will gain experience in a wide variety of biophysical techniques that are especially relevant to pre-clinical drug development. Project Title: Reporting bias - Can we trust medical science? Supervisor: Simon Kolstoe Project Brief: Reporting bias occurs when the decision of how to publish a study is influenced by the direction of its results. It is a well-recognized issue that is extremely topical as incomplete or misleading reports of trials and experiments have the potential to undermine evidence based medicine. Although the problem is becoming better known, it is still not clear what the solution might be. This is mainly because previous work has shown how difficult it is to even know that some trials have occurred let alone getting access to the original protocols to determine if the trials have been communicated accurately. This project will continue work looking at clinical projects submitted to an ethics committee and determining whether the researchers publish the results, and if so if they publish the originally specified outcomes. The project will suit students with a science background who are seeking to move into journalism, medical writing, science communication and/or regulatory and government bodies. Published work from previous MRes student: Begum R. and Kolstoe S.E. (2015) Can UK NHS research ethics committees effectively monitor publication and outcome reporting bias? BMC Medical Ethics 16:51. DOI: 10.1186/s12910-015-0042-8 Project Title: Consistency in research ethics review Supervisor: Simon Kolstoe / David Carpenter (School of Social, Historical and Literary Studies) Project Brief: Consistency is taken to mean that, for any specific application, Research Ethics Committees (RECs) give the same decision for at least roughly the same reason. RECs have occasionally been criticised for exhibiting an unjustifiable level of variation or inconsistency in their decisions. This is supported by academic papers that discuss variation in decision-making by RECs as well as evidence provided by the National Research Ethics Service’s Shared Ethical Debate exercises (ShED). Recent ShED reports have shown that presenting RECs with the same application results in a range of opinions being given, both in terms of opinion type (provisional, unfavourable, favourable (+/- additional conditions) etc.) and the reasons cited for their opinion. This project will use the method of thematic analysis to analyse data from ShED’s in order to determine key themes that lead to REC inconsistencies. The project will suit students with a science background who are interested in learning about qualitative research and perhaps with an interest in science policy. Project Title: Epitope labelling at endogenous loci using gene editing (2 projects) Supervisor: Professor Matt Guille Project Brief: Proteins are the major “doing molecules” in cells and visualising them relies on antibodies. For many key proteins however effective antibodies cannot be raised consistently; this has been identified as a major problem for biomedical science. Introducing genes/mRNAs encoding epitope-tagged versions of proteins has been a way of overcoming this, but it has limitations because the expression of these tagged proteins is not at endogenous levels and is unlikely to be in the precise cells expressing the target protein. To overcome this we have used gene editing to introduce an HA-tag to the gata2 locus; we need now to test if other loci can be similarly targeted, optimise the pipeline for producing these gene edited, transgenic animals and test whether these proteins can be visualised using an anti-HA antibody. The students will learn gene editing, microinjection, embryo culture, mutant screening, advanced experimental design, western blotting and immunostaining. Project Title: The Activation Mechanism of an Arthritis-Related Metalloproteinase Supervisor: Dr Andy Pickford Project Brief: A common pathological feature of the chronic inflammatory condition rheumatoid arthritis (RA) is the gradual destruction of the articular cartilage that lines the synovial joints of the body. One of the predominant macromolecular components of cartilage is fibrillar collagen. The enzymes responsible for breaking down this collagen in RA are members of the matrix metalloproteinase (MMP) family. These collagen-degrading MMP enzymes are secreted by cells as inactive zymogens which are then activated in the extracellular space. Therefore, the mechanism of activation of these collagenases is of great biomedical significance. Thus, the objective of this project is to investigate the mechanism by which the collagenase MMP-1 is activated by a variety of other proteases. A range of biochemical and biophysical techniques will be used in this study including site-directed mutagenesis, protein expression, chromatography, SDSPAGE, surface plasmon resonance (SPR) and NMR spectroscopy or x-ray crystallography. The project would suit a biology/biochemistry graduate interested in enzyme mechanisms and structure-function relationships. Project Title: X-ray Crystallography and NMR of Matrix Metalloproteinases Supervisor: Dr Andy Pickford / Dr John McGeehan Project Brief: Matrix metalloproteinases (MMPs) are a class a degrading enzymes that are involved in emryogenesis, development and tissue repair, but are also implicated in a number of diseases such as cancer, arthritis and fibrosis. The enzymes are synthesised as inactive precursors (zymogens) and then activated once secreted from the cell. This project will use X-ray crystallography and/or NMR spectroscopy to characterise wild-type and mutant MMPs, both in the zymogen and mature state. The student will also gain experience in recombinant protein expression, protein folding and purification. The project would suit a biology/biochemistry graduate interested in protein structure-function relationships and mechanism underpinning health and disease. Project Title: Synthetic Biology - designed mini-collagens for bio-research Supervisor: Dr Andy Pickford Project Brief: As part of the extracellular matrix, collagens provide physical support to tissues and the body as a whole. Their fibrillar nature provides immense rigidity and tensile strength but, from a research perspective, makes them particularly difficult to investigate their functional properties at the molecular level. The objective of this project is to engineer, using recombinant expression from the methylotrophic yeast Pichia pastoris, shortened “mini-collagens” that have improved solubility compared to their full-length, wild-type counterparts. This will allow functional investigations of sequences of biological importance along the triple helix. The project will involve genetic manipulation of yeast, protein expression and purification, and structural and functional analysis of the mini-collagens using a variety of biophysical and biochemical techniques. This research project would suit a biology, biochemistry or biotechnology graduate interested in molecular biology, tissue engineering and structure-function relationships in proteins. Project Title: Role of Proteases in Periodontal Disease Supervisor: Dr Andy Pickford / Dr Kristina Wanyonyi (Dental Academy) Project Brief: The project will involve the development and application of methods for the quantitative analysis of proteases involved in the progression of gum disease (gingivitis) into destructive periodontal disease, the leading cause of tooth loss in the developed world. We want to establish whether a “bio-signature” of host matrix metalloproteinases (MMP) expression could predict which patients with poor dental hygiene will develop periodontal disease. The MRes project will develop techniques required to detect and quantify messenger ribonucleic acid (mRNA) transcripts encoding for matrix metalloproteinases (MMPs) in human saliva samples, and the subsequently translated enzymes and proenzymes. A range of biochemical and biophysical techniques will be used in this study including protein expression, chromatography, SDS-PAGE, Western blotting, quantitative PCR and surface plasmon resonance (SPR). The project would suit a biology/biochemistry graduate interested in protein structure-function relationships and mechanism underpinning health and disease. Project Title: Investigating metabolite-RNase communication Supervisor: Prof. Anastasia Callaghan Project Brief: Understanding how metabolism is controlled within a cell is fundamentally important and is directly applicable to medical, environmental and biotechnological advances. Our studies have recently identified that a molecule of central metabolism interacts with an RNase and affects its ability to destroy mRNA. This project will unravel some of the details of this newly discovered mechanism and investigate whether it represents a conserved metabolite-RNase communicative link in prokaryotes and eukaryotes. Project Title: Developing novel technologies for the study of RNA-interactions Supervisor: Prof. Anastasia Callaghan Project Brief: With their versatile functions and the recent explosion of interest in transcriptomics, RNAs, and their interactions with proteins, nucleic acids and small molecules, are currently the subject of intense scientific research. RNA may represent an, as yet, untapped resource in the search for novel pharmaceutical drug targets. Characterization of bio-molecular interactions with RNAs is becoming increasingly necessary as the repertoire of RNA functions continues to expand. Such interactions are regularly investigated using sensor technique instrumentation that involves the immobilisation of one of the molecules being studied. This project will involve working on developing a novel method to tag RNA molecules for sensor-surface immobilization in order to support bio-molecular interaction studies of this important family of biological molecules using sensor technique instrumentation. Project Title: Studying a novel mechanism linked to pathogenic bacterial virulence Supervisor: Prof. Anastasia Callaghan Project Brief: With antibiotic resistance on the rise, research into understanding the workings of bacterial organisms is crucially important, as are new approaches to combating the infections they cause. The aim of this project is to therefore increase our understanding of a recently discovered mechanism of genetic regulation which has potential applications in the field of antibacterial research. Specifically, the interplay of small non-coding RNAs, their mRNA targets, and an RNA chaperone protein, result in a finely balanced mechanism of communication leading to either transcript destruction, or stabilization and subsequent translation. The project will address how this communication occurs and whether this mechanism, with a direct impact on pathogenic bacterial virulence, can be exploited in the search for novel antibacterial approaches and/or targets. Project Title: Investigating the inhibition of the novel antibacterial target, RNase E Supervisor: Prof. Anastasia Callaghan Project Brief: In an era of increasing antibiotic resistance, new antibacterial targets are urgently required. Found only in bacteria, the essential endoribonuclease RNase E represents such a potential target. Extensive structural characterisation of RNase E from the model organism, Escherichia coli, has provided molecular level details of the functioning of the protein, enabling the first steps, to be taken towards structure-based inhibitor design. This proposal focuses on furthering the understanding of the inhibition of E. coli RNase E and its homologues in pathogenic bacteria. Expanding on existing in silico inhibitor design studies, potential small molecule inhibitors will be tested experimentally and their mechanisms of inhibition characterised prior to assessment of in vivo effectiveness. Project Title: Understanding novel bacterial molecular switches applicable to synthetic biology Supervisor: Prof. Anastasia Callaghan Project Brief: Bacteria can use specific molecules to either promote or repress protein translation through a novel post-transcriptional mechanism. This ability to turn genes on or off at the right times and at the right levels demonstrates a potential role for these specific molecules as molecular switches, ripe for exploitation within a synthetic biology context. This project will seek to explore the application of these specific molecules as artificial molecular switches. Project Title: The Role of variant histones in Xenopus early development. Supervisor: Fiona Myers & Matt Guille Project Brief: The functional & developmentally differential control of specific histone variants during early development will be investigated using a combination of assays: xChIP, ChIPseq, immuno-histochemistry, in-situ hybridisation, morpholino knockdown, RNA-seq and CRISPR/Cas9 gene editing.This work in collaboration with Professor Guille’s lab will use the Xenopus model system in order to study variant histones in an in vivo environment and will elucidate their roles in key developmental processes. Project Title: Role of histones and histone variants in the first stages of reprogramming fibroblasts into pluripotent stem cells. Supervisor: Fiona Myers & Colyn Crane-Robinson Project Brief: Changing cell fate holds the potential for therapy in regenerative medicine. If a patient’s cells, e.g. skin fibroblasts, could be turned into the cell type in need of regeneration all problems associated with tissue rejection would be eliminated. For this to develop we require a full understanding of how the gene expression profile of the initiator cell is altered to determine cell fate. This project in collaboration with Prof Colyn Crane-Robinson will investigate the role of both modified and variant replacement histones in the earliest stages of re-programming fibroblasts into pluripotent stem cells. Project Title: Epigenetics in Lomnoria (environmental epigenetics) Supervisor: Tim Hebbes and Simon Cragg Project Brief: The epigenome provides a series of codes, over and above the genome sequence, that regulate gene expression. Increasingly we have become aware that environmental factors such as diet, stress and exposure to toxicants all influence the epigenome and gene regulation. The wood-boring organism Limnoria has a number of different cellulase enzymes, the expression of which are altered by diet. The aim of the project is to understand the regulation of the digestive enzyme glycosyl hydrolase (GH7) gene, by analysing the epigenetic status of its chromatin from animals fed on different woods. The project will use a number of marine and molecular biology techniques including western blot, immunohistochemistry and cloning. The project will further our understanding of how particular environmental cues change the epigenetic status and influence gene regulation. The application of epigenetic approaches to a marine organism is novel and offers opportunities for pioneering work. Project Title: Enzyme kinetics and ligand binding of DNA endonucleases, exonucleases and ligases. Supervisor: Dr Darren Gowers Project Brief: My research group focus on understanding the kinetics and binding of enzymes that interact with specific sequences or specific structures of DNA. These include a large number of DNA restriction enzymes (such as SfiI or BbvCI) that have to locate a specific target site; exonucleases (such as lambda exo) that have to locate a DNA end, and ligases (such as E.coli DNA ligases A and B) that have to locate a specific nick site within a long DNA chain. The work will involve growing E.coli cultures, harvesting and purifying proteins, using PCR, checking enzyme purities on SDS gels, designing experiments, running accurate timecourses, analysing DNA fragments by electrophoresis through agarose or polyacrylamide, gel imaging, quantitation and data fitting. Project Title: The effect of pollution on the ecology of plankton in Langstone Harbour Supervisor: Dr Joanne Preston Project Brief: Langstone Harbour receives a range of anthropogenic inputs, including frequent storm water discharges (a mixture of rain and untreated sewage). The increased nutrient status associated with this pollution can drive phytoplankton blooms and lead to decreased water quality. This project will examine the relationship between nutrient status, phytoplankton community and zooplankton diversity, with a focus on the larvae of ecologically important marine species (the native oyster Ostrea edulis and the invasive mollusc Crepidula fornicata). The project will involve boat and fieldwork, and utilise microscopy, flow cytometry and molecular techniques to analyse the plankton community. Project Title: Analysis of Ostrea edulis larval recruitment and settlement in the Solent. Supervisor: Dr Joanne Preston Project Brief: Historically the Solent supported one of the largest native Oyster (Ostrea edulis) fisheries in Europe. The oyster population suffered a catastrophic crash in 2006 due to overfishing, habitat destruction, pollution and potentially climate change impacts. The recovery of the native oyster has been poor despite closure of the fishery, and a large project is underway to restore the native oyster population and oyster seabed habitat. This project will be part of the larger restoration work, and will analyse the onset and duration of spawning, planktonic larvae behaviour and settlement rates of juvenile oyster spat. The project will involve boat and fieldwork, and utilise microscopy, flow cytometry and molecular techniques to analyse the life history of this ecologically and commercially important species. Project Title: Microplastic uptake in filter feeding marine invertebrates in the Solent Supervisor: Dr Joanne Preston Project Brief: Plastic pollution is pervasive in the marine environment and has devastating impacts on marine ecosystems and the organisms therein. Often, the first entry into the animal food web is via invertebrate filter feeders. This project will examine a range of filter feeding marine species (sponges, oysters, mussels, tunicates) for their microplastic uptake and retention. The microplastic content of the water will also be analysed. The project will involve boat and fieldwork, and utilise microscopy, fluorescent microscopy, flow cytometry and aquarium based experiments. Project Title: Microbial populations within flower nectar Supervisor: Dr Joy Watts Project Brief: Little is currently know about the bacterial communities present in different plant species nectar. These bacterial populations from a number of different plants (in collaboration with Ventor Botanical Gardens) will be examined for diversity and species composition. Additionally temporal studies will be performed to examine changes in the microbial population over the flowering season culture based and molecular techniques. Project Title: Microbial settlement populations and community diversity on historically relevant stone. Supervisor: Dr Joy Watts Project Brief: A number of local heritage sites are involved in the preservation and conservation of historically important stone relics and sites; however this stone can be colonised and damaged by complex microbial populations. In this study the microbial community will be analysed from a number of samples in different historically important locations to try and identify key members of the community and to determine their role in stone degradation and methods of preservation. Project Title: The effect of marine litter on water quality in Langstone Harbour Supervisor: Joy Watts/ Michelle Hale Project Brief: Using a range of techniques such as direct counts, fecal coliform numbers and DNA extraction and community analysis the effects of marine litter on microbial community stability and function in Langstone harbour will be examined. Microbial source tracking from sewage outfall and sediment resuspension will also be an area of focus. This project will run in partnership with Southern Water. Project Title: The effect of marine litter on water quality in Langstone Harbour Supervisor: Ian Hendy/ Paul Farrell Project Brief: Surveying the incidence of marine plastic litter in Langstone Harbour. Research questions are: How is the marine litter distributed along the shoreline, the composition of this marine litter (What percentage is wastewater related?). The age of the marine litter (time at sea) and what is the likely origin of the litter? (Land based, boats/marine industry, sewage outfall, storm water discharges etc.) The project will involve working in collaboration with southern water, and another MRes student looking at water quality and microbial aspects of litter. The project will involve extensive boat and shoreline fieldwork. Project Title: The translational control of retinoid receptor expression Supervisor: Colin Sharpe Project Brief: The retinoid receptors mediate retinoid signaling, which, in the early embryo, is important for axial patterning and for neuronal differentiation. Examination of the transcripts that encode the retinoid receptor RAR alpha 2 show that it has an extensive 5’ untranslated region (UTR) that precedes the open reading frame encoding the receptor. Preliminary experiments show that the 5’UTR determines when, during Xenopus development, RAR alpha 2 mRNA is converted into protein. Sequence analysis indicates that this mechanism is conserved across the vertebrates. The aim of the project is to determine the regions of the 5’UTR that mediate this regulation and identify the factors in the embryo that determine when the mRNA is translated. This will involve molecular biology to construct minigenes that can be injected into Xenopus embryos and then Western blotting as an assay for protein production. The project requires an interest in molecular biology, gene expression and embryology. Project Title: The role of RXR in the expression of ApoE and ABCA1, key proteins in the clearance of Alzheimers amyloid protein plaques. Supervisor: Colin Sharpe Project Brief: Xenopus embryos will be used as a tool to investigate the expression of genes involved in the clearance of amyloid plaques. ApoE, a component of the high density lipoprotein that clears cholesterol from the vasculature, is also important in clearing amyloid protein in the brain. Its assembly and export from glial cells in the brain is mediated by the ABCA1 protein. In the mouse, both ApoE and ABCA1 are regulated by the nuclear receptor, RXR, a transcription factor. We have shown that both ApoE and ABCA1 are expressed in the Xenopus embryo as the neural tube forms. The first aim of the project is to look at the details of this pathway; when and where are these genes expressed in normal development. RXR acts in combination with the transcription factors LXR or PPAR gamma. The second aim will be to knockdown expression of one or more of these genes in the Xenopus embryo using the CRISPR-Cas9 system. Finally, bexarotene, an RXR agonist is a potential treatment for Alzheimers and works by activating the expression of RXR and ABCA1. The final aim is to examine the effects on neural development of Bexarotene added to Xenopus embryos. Project Title: Improving urban air-quality using plants Supervisor: Matthew Tallis and Mike Fowler Project Brief: This project will involve characterising the composition and deposition rates of a range of urban air-pollutants to different forms of urban vegetation. Verge-plants and street trees will be examined in both the urban environment and under controlled conditions. Particulate-matter air-pollution is responsible for approximately 50, 000 premature deaths each year in the UK and ranked the 13th leading cause of human mortality worldwide. Urban vegetation is a very effective way of filtering particulate pollution from the atmosphere so saving lives and money. Key to the effectiveness of this approach is identifying the best vegetation forms for specific environments. This project will help identify the vegetation forms needed to optimise particulate pollution removal in urban environments. The project would suit a student with interests in sustainability, plants and air-pollution. Project Title: Improving the health benefits from greenhouse grown crops Supervisor: Matthew Tallis and Mridula Chopra Project Brief: This project will investigate the effect changes in growth, harvest and storage conditions have on the shelf-life and nutritional content for a range of greenhouse grown crops. Dietary consumption of salads, fruits and vegetables have been linked to human health benefits by providing beneficial nutrients and antioxidant compounds. However, the nutrient content of such crops can change depending on growth and storage conditions. The aims of this project are to quantify the impacts different growing, harvest and storage conditions have on yield, antioxidant content and shelf life of selected greenhouse grown crops. This project would suit a student with interests in plants, agronomy and nutrition. Project Title: Investigating microbial communities found on shark egg cases Supervisor: Dr Maria Salta Project Brief: Microbial communities found on shark egg cases are largely unexplored. This project will use culture techniques, microscopy and molecular tools to analyse bacterial communities found on elasmobranch egg cases such as Scyliorhinus canicula. Project Title: Impact of Climate Change on Marine Biofilm Dynamics and the Effectiveness of Antifouling Coatings Supervisor: Dr Maria Salta and Dr Federica Ragazzola Project Brief: Marine biofilms (BF) are composed of a high diversity of microorganisms such as bacteria and microalgae. In the marine environment it has been shown that often BF play a key role in colonisation processes of larger organisms such as algae and barnacles (collectively known as biofouling). Biofouling can have a detrimental effect on manmade structures: on ship hulls it leads to increased skin friction, higher fuel costs and increased CO2 emissions; it has been shown that the primary associated costs with fouling is due to increased fuel consumption linked to frictional drag (estimated to be $56 million per year for a mid-sized ship). The aim of the project is to identify the impact of climate change on biofilm communities attached on AF surfaces, with the additional aim of understanding how AF coatings themselves are affected by climate variations. Project Title: Cell Biology of neurogenesis Supervisor: Frank Schubert Project Brief: In the embryonic vertebrate brain, neurogenesis is initially restricted to a few clusters of cells. FGF signalling is a major factor in suppressing neurogenesis in other parts of the brain. The molecular mechanisms mediating the FGF signal, however, are unknown. The project is based on a previous MRes project that showed that two signalling pathways (Ras/MAPK and p38/MAPK) act in parallel to inhibit neurogenesis in the midbrain. Furthermore, we know the immediate transcriptional changes following FGF receptor inhibition from our RNA-Seq analysis. By using a combination of pharmacological and molecular genetics approaches, this project aims at elucidating the gene regulatory network regulating the onset of neurogenesis. Project Title: Developmental biology of drug-associated autism Supervisor: Frank Schubert Project Brief: Autism spectrum disorder (ASD) is estimated to affect more than 1% of the population in the UK. Possible causes of ASD include genetic predisposition and maternal infections, but also prenatal exposure to some teratogens. Reports in the literature suggest that a sensitive period is early in pregnancy, coinciding with the first neurone differentiation in the embryonic brain. Preliminary results in our lab indeed indicate changes in neurogenesis and patterning gene expression following treatment with thalidomide or valproic acid. This project aims to characterise the developmental changes caused by the drugs, and to expand the study to other drugs not currently associated with ASD, like selective serotonin re-uptake inhibitors (SSRIs). Project Title: Cell polarity during vascular ingression Supervisor: Frank Schubert Project Brief: The blood supply of the central nervous system is provided by mesodermderived endothelial cells. These initially aggregate around the neural tube to form the perineural vascular plexus (PNVP), but eventually penetrate the basal lamina and ingress radially into the neural tube. Each angiogenic sprout is led by a specialised tip cell, followed by stalk cells. Previous work in the lab has described the process anatomically and has characterised the activity of matrix metalloproteinases. In contrast, little is known about the polarity of the PNVP, tip cells and stalk cells. The aim of this project is to study the location of apical or basal marker proteins during vascular ingression by immunofluorescence. Project Title: Axon guidance signals that organise the early axon scaffold in the vertebrate brain Supervisor: Frank Schubert Project Brief: The first neurones that differentiate in the embryonic vertebrate brain establish an evolutionary conserved array of longitudinal, transversal and commissural axon tracts, the early axon scaffold. Despite the stereotypical arrangement of these tracts, little is known about the signals that underlie the guidance of the axons. We have characterised the expression of the main axon guidance molecules in the early brain, providing candidate genes for analysis. The aim of the project is to test the function of these genes in the guidance of early axons by in-ovo electroporation and loss-of-function approaches. Project Title: Turning mats into money Supervisor: Dr Gordon Watson Project Brief: Protecting and enhancing transitional and coastal water (TAC) ecosystems are essential to growing a sustainable blue economy (e.g. fisheries, tourism), meeting conservation objectives (e.g. protecting habitats/birds) and improving public health (e.g. shellfish consumption). However, all urbanised TAC waters have elevated nutrient levels leading to poor water quality caused by inputs of fertilizers, livestock and human waste. This results in the excessive growth of plant life (termed eutrophication). Coastal eutrophication results in the rapid growth of green seaweeds on intertidal mudflats forming mats 10 cms deep and covering thousands of hectares. These have significant ecological impacts (a key measure for not achieving GES [Good Ecological Status] via the WFD [Water Framework Directive]), as well as economic and human health issues. This project will develop and test innovative, sustainable and cost-effective methods that will rapidly reduce algal mat coverage of these habitats and contribute to reductions in nutrient levels. Feeding algal mats to polychaete worms and converting these to AC (aquaculture) feed will be tested under controlled conditions to maximise growth and assess the conversion of algal biomass to polychaete biomass. Project Title: Novel Mechanism of Antibiotic Resistance in a New Forest Pond Supervisor: Dr James McClellan Project Brief: Antibiotic resistant microbes are a major problem, tackling which will require the discovery of new antibiotics. Recently we have found small rRNA-like molecules in a freshwater site in the New Forest, and we hypothesise that these may be “decoys”, providing a novel resistance mechanism against antibiotics that target the ribosome - 50% of known antibiotics do this. The project is to further characterise these molecules, and to isolate any associated antibiotic-producing genes. Project Title: Structural Dynamics of CNG repeats associated with human genetic disease. Supervisor: Dr James McClellan Project Brief: Triplet repeats are associated with genes that influence development of large cells such as nerve and muscle. We have shown that such repeats exhibit structural dynamism depending on their length, and environmental conditions including temperature. Since long repeats are associated with neuromuscular diseases, it is important to deepen our understanding of these structural dynamics, which are the focus of this project. Project Title: Intersexuality and metal pollution in amphipods crustaceans Supervisor: Alex Ford Project Brief: Some recent studies have linked reproductive abnormalities such as intersexuality in amphipods to pollution and parasites. This study aims to determine the metal concentrations and incidence of intersexuality in amphipods clean and polluted coastal locations. Project Title: Neuroendocrine disruption in crustaceans Supervisor: Alex Ford & Jerome Swinny Project Brief: Studies in our labs have recently found that antidepressants (SSRIs) can impact the behaviour of crustaceans at environmentally relevant concentrations. The aim of the study is to ascertain whether exposure to SSRIs alters the serotonergic and dopaminergic activity in shrimp using immunohistochemistry. Project Title: Phylogeny of Antarctic coralline algae Supervisor: Dr Federica Ragazzola and Dr Jo Preston Project Brief: The Corallinales, along with the Sporolithales (Corallinophycidae, Rhodophyta), is a red algal order characterized by the presence of Mg-calcite in their cell walls. This calcification capacity confers them a crucial ecological role by creating new habitats sand therefore increasing biodiversity. However, coralline identification is complicated by phenotypic plasticity depending on environmental conditions as well as the need for decalcification prior to the observation of anatomical features. The aim of this project is to create a phylogenetic tree of Antarctic coralline algae by combining morphological (histology, SEM) and genetic analysis Project Title: Carbonate changes of different populations of Corallina officinalis under future climate change scenario Supervisor: Dr Federica Ragazzola, and Dr Gianluca Tozzi (Engineering) Project Brief: Coralline algae are a significant component of the benthic ecosystem. Their ability to withstand physical stressed in high energy environments relies on their skeletal structure which is composed by high Mg calcite. The aim of this project is to determine the changes in the calcium carbonate composition of specimens cultured under future climate change scenario using ImageJ software (for the linear growth rates) and a non-destructive, high resolution quantitative volumetric investigation (microCT). The project will be mainly computer based. Project Title: Plasticity of Corallina officinalis in long term experiments Supervisor: Dr Federica Ragazzola Project Brief: Coralline algae are a significant component of the benthic ecosystem. Their ability to withstand physical stressed in high energy environments relies on their skeletal structure which is composed by high Mg calcite. The change in Mg alters the material properties of the calcite: increase the solubility of the skeleton and altering the mechanical properties as a Mg-enriched matrix increases deformation resistance. The aim of the project is to analyse the phenotypic plasticity of coralline algae from a long term culturing experiment using Scanning electron microscopy and Energy dispersive spectroscopy Project Title: Structural integrity of different population of Corallina officinalis Supervisor: Dr Federica Ragazzola and Dr Jurgita Zekonyte (Engineering) Project Brief: Coralline algae are a significant component of the benthic ecosystem. Their ability to withstand physical stressed in high energy environments relies on their skeletal structure which is composed by high Mg calcite. The change in Mg alters the material properties of the calcite: increase the solubility of the skeleton and altering the mechanical properties as a Mg-enriched matric increases deformation resistance. The aim of this project is to determine the changes in plasticity, elasticity and hardness of specimens cultured under future climate change scenario using nano-indentation. This project will be mainly computer based Project Title: The effects of antidepressants on embryonic development and adult behaviour in zebrafish Supervisor: Alex Ford & Matt Parker Project Brief: Antidepressants can be detected in aquatic ecosystems at concentrations believed to be causing harm to wildlife. This study aims to investigate the effects of fluoxetine on early embryonic development and adult behaviour using zebrafish as a model species. END OF DOCUMENT