GRS studentships

Despite major advances in its early detection, preventive measures and therapeutic options, colorectal cancer remains one of the most commonly diagnosed cancer and a leading cause of cancer deaths worldwide. In order to reduce deaths due to colorectal cancer, it is essential to discover additional biomarkers of diagnostic, prognostic and therapeutic values in such patients. In the past few years, we have been investigating the role of human epidermal growth factor receptor (EGFR) family members in the progression of a wide range of cancer, in particular colorectal cancer, their prognostic significance and predictive value for response to targeted therapeutic regimens. More recently, we developed several in house monoclonal antibodies (mAbs) against antigens with high levels of expression on the cell surface of human pancreatic cancer cells and other cancer cells, including colorectal cancer.

This three-year full-time PhD project aims to investigate the relative expression and prognostic significance of such antigens in patients with colorectal cancer. We shall also investigate the relative expression of such antigens on the cell surface of human colorectal cancer cells and the therapeutic potential of such mAbs when used alone and in combination with the small molecule tyrosine kinase inhibitor (TKIs) or cytotoxic drugs on the growth and migration of human colorectal cancer cell lines and their drug-resistant variants. The results of this investigation should not only help to define the role of such antigens in the malignant behaviour of colorectal cancer but also the therapeutic advantages of mAbs targeting such antigens when used in combinations with other drugs.

First supervisor: Dr Said Khelwatty s.khelwatty@kingston.ac.uk

60% of all clothes contain some synthetic fibres. Currently, the main disposal methods used are landfill or incineration, both of which cause serious environmental damage so a cleaner and more sustainable alternative is required. With over 100 billion items of clothing produced every year there is an urgent need to find sustainable methods of disposal. We have a strong focus on developing a system that would be scalable for industrial use in LMICs, as the majority of the environmental damage incurred through the textile industry is borne in developing countries.

This project builds on our current work investigating filamentous fungi as a possible means of bioremediating textile waste. Our work to date has identified several candidate species of fungi that grow well on fabric with varying synthetic content, although the mechanisms and processes used by the fungi in this process remain unknown. This project will seek to identify specific proteins and pathways utilized by the fungus during the bioremediation process, and investigate the potential for biodegrading heterogeneous textile waste. The project will involve some bioinformatic analysis of fungal genomes, fungal culture, imaging, metabolomics and proteomics to investigate the potential of different species to metabolise a variety of fabrics. This is a new field of research with many unknowns, so the PhD candidate must be willing to undertake protocol development and have excellent problem-solving skills.

First supervisor: Dr Suzy Clare Moody s.moody@kingston.ac.uk

The initiation and progression of cancer has become an extensively-studied topic due to the debilitating effects of the disease and its increasing incidence over the past 50 years. It is well known that signalling pathways may regulate the formation and progression of cancer, and one of these pathways is the Hippo Signalling Pathway. The Hippo Signalling Pathway is an evolutionary-conserved pathway with a key role as a regulatory pathway in organ growth control and maintenance (Piccolo et al 2013). The two main effectors, YAP and TAZ if dysregulated, can result in over-proliferation and uncontrolled cell division and ultimately develop into advanced malignancy (Harvey et al 2013, Pocaterra et al 2020). YAP and TAZ are potent oncogenes found to be upregulated in many cancers and maybe thought of as therapeutic targets due to the fact that inhibition of these genes can inhibit or suppress cancer cell growth and migration (Lo Sardo et al 2018, Yip et al 2021, Zanconato et al 2016). An important cancer which is affected by YAP/TAZ upregulation is colorectal cancer (Ou et al 2017, Jin et al 2021). The triggers that cause YAP/TAZ to become upregulated is one of the most widely studied aspects of cancer therapy to date, with various studies showing different theories, one thing that is thought is that a possible role for growth factor signalling may play a critical role in this regulation (Hsu et al 2019, Huang C, et al 2020).

Serotonin (5-hydroxytryptamine, 5-HT) is a classical neurotransmitter in the central nervous system which is also known as a local mediator in the gastrointestinal tract. Serotonin is a biogenic monoamine synthesised from the essential amino-acid tryptophan. This amino acid is primarily obtained from diet. Serotonin has also been recently implicated as a potent growth factor for several human cancers. Serotonin is thought to encourage cancer cell proliferation, metastasis, and formation of tumour blood supply initiation (angiogenesis) (Liang et al 2013, Sarrouilhe et al 2019, Peters et al 2020). As potentiation of serotonin signalling results in enhanced intestinal epithelial proliferation, there is a thought that serotonin signalling may influence key cancer proliferative pathways, and the serotonin receptor 5-Hydroxytryptamine receptor 2B (5HT2b) may play an extensive role in this progression (Soll et al 2010). As YAP/TAZ are key proteins in encouraging cancer proliferation and inhibition of apoptosis as well, then it is an obvious pathway to investigate and whether 5HT2b receptor regulation crosstalks with YAP/TAZ and the Hippo signalling pathway. Furthermore, studies show that knockdown of 5-HT2b in late-stage colitis-associated cancer (CAC) can inhibit further tumour growth (Mao et al 2022).

Aims of the project

The aims of this project are twofold. The first aim is to elucidate the link between cancer receptor signalling primarily mediated by 5-HT2b by using therapeutic targets which may act as antagonists of these receptors.

The second aim of this project is to analyse if 5-HT2b and any effect on signalling may be mediated by the Hippo Signalling Pathway and whether there is a crosstalk between classical cancer signalling pathways including MAPK and PI3k/AKT signalling (Dhillon et al 2007, Jiang et al 2020), both of which encourage regulation of cellular proliferation and cellular survival. Inhibition of key cancer causing/progression pathways by inactivating serotonin receptor signalling might allow the development of key therapeutics to target cancers via key receptor signalling. Serotonin is also evolutionary conserved from simple organisms such as Drosophila melanogaster and Planariidae and is important in cellular regeneration (Sarkar et al 2019) in common with the Hippo signalling pathway, thus it would be interesting to analyse the link in vivo and would be an essential aspect of the project.

This project will provide extensive training in a wide range of cell and molecular biology, Biochemistry and analytical techniques, including but not limited to Immunoblotting, Immunofluorescence, confocal microscopy, PCR, scratch-based assays, Mass Spectroscopy and RNA seq analysis.

Applicants should have a first or upper second-class honours degree in a relevant area to the project. A masters degree or equivalent qualification or other evidence of research skills and experience is preferred.

First supervisor: Dr Ahmed Elbediwy a.elbediwy@kingston.ac.uk

The innate immune system can display characteristics of immunological memory. This phenomenon, termed "trained immunity", refers to the long-term functional reprogramming of innate immune cells after the encounter with infectious or non-infectious agents that influences their capacity to respond to a secondary stimulus. Many infectious stimuli, including bacterial or fungal cells and their components (LPS, β-glucan, chitin) are considered potent inducers of innate immune memory, enhancing the pro-inflammatory effects of the innate immune system. However, innate immune cells also arbitrate anti-inflammatory responses, therefore following exposure to appropriate cues they can be trained to be anti-inflammatory.

Research in the past decade has highlighted the broad benefits of pro-inflammatory trained immunity for host defence in the context of infectious disease. However, anti-inflammatory trained immunity could on the other hand have a protective influence against the development of immune-mediated diseases, of important therapeutic implications. Diseases mediated by a dysregulated immunity, such as inflammatory bowel disease, rheumatoid arthritis or asthma, are often treated with immunosuppressive drugs, which, although effective, are not voided of serious side effects. We have previously shown that immunomodulatory strategies that, instead of suppressing, promote the body's natural protective innate immune responses can effectively ameliorate disease progression in models of inflammatory bowel disease. 

Innate immune memory may also play a role in the connection between early life exposure to microbes and patterns of disease susceptibility. Of note, epidemiological studies reveal a significantly lower incidence of immune mediated diseases in developing countries with a high prevalence of parasite infections. Thus, it is possible that parasites could induce an anti-inflammatory training program in our immune system that may be key in preventing the development of those conditions.

This project aims to examine the hypothesis that helminth-derived products can effectively induce a training program in macrophages, reprogramming them to be more anti-inflammatory in response to a secondary inflammatory stimulus. A secondary aim in the wider project will be to establish if anti-inflammatory trained immunity induced by helminth products confines a reduced susceptibility to inflammatory bowel disease.

First supervisor: Dr Nati Garrido Mesa n.garridomesa@kingston.ac.uk

Plastic production is on the rise and pollution derived from it is increasing. The scientific community is trying to understand how plastic degrades and fragments into micro, nanoplastics and chemical degradation products. UV from the sun is a main factor in the degradation of plastics and the state of the ozone layer may be affecting the degree of the degradation and ultimately the environmental impact and harm to organisms. The degradation of plastics will also affect plastic infrastructure outdoors. The microplastic problem has been associated with microbeads in personal care products, however we know now that these are not the main problem; fibres from textiles and fragments from bigger plastics are thought to be the most hazardous forms of plastic and they also constitute the most common type of microplastic in water, soil and organisms. The size, composition of the plastic particles and their weathering degree are expected to play a role in their impact. 

The research question we pursue in this PhD is whether plastic fragments and fibres suspended in the atmosphere can have a detrimental effect related to climate change and organisms. This ambitious PhD project will set up experiments to know more about this unexplored area. This will be an interdisciplinary project with components of analytical chemistry (main area), physical chemistry and toxicology. Specifically, the PhD will involve the use of liquid chromatography-mass spectrometry and a wide range of microscopes. This project seeks to investigate the link between plastic pollution, greenhouse effect and the ozone layer. Members of the supervisory team have track records of working with microplastic pollution and contribute to the United Nations Environment Programme- Environmental Effects Assessment Panel working on the direction of this PhD.

First supervisor: Dr Rosa Busquets r.busquets@kingston.ac.uk

In recent years occurrence of antibiotics in aquatic systems has attracted significant attention, particularly in rivers which receive sewage treatment effluent where they have been found to bioaccumulate in aquatic organisms, albeit in trace amounts. Antibiotics enter wastewater streams, mainly through their usage/excretion and inappropriate disposal and undergo degradation during wastewater treatment.

Existing data on pharmaceuticals/antibiotics removal/degradation in wastewater treatment is limited and show highly variable removal efficiencies, possibly due to the difference in technologies and operating conditions used in wastewater treatment plants (WWTPs). Clearly, there is lack of understanding the link between antibiotics usage and their environmental impact in receiving waters following sewage effluent discharges. This is important to understand, particularly the extent to which antibiotics are degraded/removed during wastewater treatment. Understanding the link between antibiotics usage and the extent of their degradation in WWTPs is essential to develop more effective wastewater treatment strategies/technologies to mitigate their environmental impact in receiving waters.

This project seeks to investigate antibiotics usage, their removal in wastewater treatment and environmental impact by determining their concentrations in sewage influents, effluents and receiving waters, with an ultimate aim of modelling the entire process (usage, degradation/removal and environmental impact). Findings from this research are likely to be useful in designing effective wastewater treatment strategies/technologies to mitigate antibiotics' impact in receiving waters. The work will target three-to-four contracting capacity WWTPs and will consider seasonality (e.g. greater use of antibiotics and high river flows in winters).

First supervisor: Professor James Barker j.barker@kingston.ac.uk

Aims and objectives

This project will prepare the first smart polymers (nanomedicines) functionalized by quinone chemotherapeutics which will be evaluated for antitumour and antimicrobial activities. The latest controlled/living polymerization induced self-assembly (PISA) techniques will be used to access nanomedicines with higher order morphologies (rods, worms, and vesicles). These morphologies are more efficient in penetrating cell membranes. Nanomedicines will be smart or (stimuli-sensitive) responding to specific pathological conditions (e.g., anaerobic conditions, pH, temperature, elevated CO2, glucose and/or lactate). Synthetic methods developed include those using benign green chemistry conditions, and radical cascades.

Training provided in:

1. Synthetic organic and polymer chemistry and associated analytical techniques (e.g., NMR, GPC, and UV, IR, and mass spectroscopy).
2. Biological evaluation methods, including cell culture, cytotoxicity measurements, western blotting, immunofluorescence, and enzyme kinetics.
3. Polymer particle analysis techniques, including Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS).

We wish to recruit PhD candidates enthusiastic about multi-disciplinary research, with a particular interest in synthetic organic, medicinal and polymer chemistry.

Background

This group has published on the discovery of heterocyclic quinone anti-cancer agents with specificity towards hypoxic cells associated with solid tumours, reductase enzymes over-expressed in cancer, and mutations in the FANC/BRCA DNA repair genes. We have developed safer nitric oxide (NO) donating vasodilators, that release NO up to 7 times faster than the commercial drug. Our passion is the synthesis of new heterocycles, which account for more than 80% of all pharmaceuticals, in particular heterocyclic quinones reductively activated in solid tumour cells. Recently, we developed heterocyclic quinone prodrugs activated by visible light, which offer potential new photodynamic therapy treatments.

First supervisor: Professor Fawaz Al-Dabbagh f.aldabbagh@kingston.ac.uk

Quantum dots (QDs) are photoluminescent nanoparticles which reside at the cutting edge of opto-electronic device development. QDs owe their remarkable photoluminescence to their small size and semiconducting properties, with each of their dimensions smaller than the Bohr radius of the parent material in a strong confinement regime.

Research efforts have focused primarily on improving optical properties, reducing "blinking" and toxicity of QD materials and improving biocompatibility. To date however, there have been very few reports of using QDs to catalyse organic transformations. In this role, QDs offer significant advantages, as they are light rather than heat-activated and straddle the gap between homogeneous and heterogeneous catalysis, meaning they are fully dispersed in the reaction solvent and easily isolable by centrifugation.

QDs are often highly susceptible to oxidation, as well as being synthesised of toxic materials. [2] The overgrowth of shell materials with similar lattice parameters and lower toxicity can preserve/enhance QD photoluminescence, prevent oxidation and inhibit leaching of toxic ions. For typical II-VI and III-V core materials (such as CdSe and InP respectively), ZnS is an excellent non-toxic, wide band-gap shell material. [2]

Early synthetic methods for ZnS shells focussed on the use of highly pyrophoric alkyl zinc and malodorous silathianes. [2] Whilst successful, these reagents require careful handling and specialist equipment (e.g. nitrogen gloveboxes) to use effectively. Since the early 2000s, alternative routes to QD shells based on the decomposition of air-stable, single-source molecular precursors emerged. In particular, inexpensive metal dithiocarbamate species which decompose cleanly into ZnS (and volatile organics) at low temperatures have moved to the fore. [3] 

In 2014, Bear, Hogarth et al. reported a method to synthesise composite QD shells on CdSe QD cores for catalytic applications. [4] Our work showed that doping copper with zinc (synthesising a CdSe/ZnS-CuS core/shell QD) had a  detrimental effect on the overall photoluminescence, introducing a second, long-lived photoluminescence feature, but was essential for catalytic activity. Catalytic activity was assessed using the "Click" reaction of phenylacetylene and benzyl azide under 254 nm irradiation, achieving ≥99 % yield over several cycles for both the 1:1 and 1:3 molar ratio of copper:zinc. To date, this is unmatched in studies where QD catalysis and the same reaction was used. It was found that copper was released into solution by ICP-OES, and therefore postulated that the QDs act as catalyst vectors rather than true catalysts, albeit with impressive turn over numbers and able to catalyse multiple reaction cycles.

We will expand this work by synthesising new metal-sulphide single-source precursors for different core/shell systems. Work will focus on adding metals to CdSe/ZnS system, and expand the number of organic reactions catalysed, looking at carbonylation and carbon-carbon bond formation. In doing this, we will be able to ascertain how well the ZnS lattice reacts to doping with different metals, which will allow investigation of the mechanism of catalysis, which is currently unexplored. This can then be applied to bespoke organic transformations.

The successful candidate will work between the Bear group at Kingston University and the Hogarth group at King's College London. They will have the opportunity to learn nano- and air-sensitive synthetic techniques, NMR spectroscopy (for in situ catalysis monitoring), ICP-OES analysis, electron microscopy and fluorescence spectroscopy. In addition, the Hogarth group has extensive experience in the synthesis of metal dithiocarbamate species required for QD shell doping, with the possibility of novel compounds to be synthesised and isolated.

Objectives:

1. Investigation of the mechanism of catalysis in metal-doped QD shell systems.
2. Explore how far the ZnS shell lattice can be doped with different metal ions.
3. Expand the number of organic reactions that can be catalysed by metal-doped QDs.

Further reading:

• [1] Quantum dots: "A review on sustainable synthetic approaches toward photoluminescent quantum dots" – W. Yang et al., Green Chem. 2021 doi:10.1039/D1GC02964A.
• [2] Quantum dot shells: "Core/Shell semiconductor nanocrystals"- P. Reiss, M. Protière, L. Li, Small 2009 5, 154-68.
• [3] Dithiocarbamate synthesis: "Dithiocarbamate complexes as single source precursors to nano-dimensional metal sulfides" - J. C. Sarker, G. Hogarth, Chem. Rev., 2021, 121, 6057-6123.
• [4] Quantum dot catalysis: "Copper-Doped CdSe/ZnS Quantum Dots: Controllable Photoactivated Copper(I) Cation Storage and Release Vectors for Catalysis" - J. C. Bear, N. Hollingsworth, P. D. McNaughter, A. G. Mayes, M. B. Ward, T. Nann, G. Hogarth, I. P. Parkin, Angew. Chem. Int. Ed. 2014, 53, 1598–1601.

First supervisor: Dr Joseph Bear j.bear@kingston.ac.uk

Background

Research in the Kadri group focuses on developing innovative chemical approaches for the discovery of novel therapeutics to address unmet global health needs. Research is multidisciplinary spanning the fields of chemical biology, medicinal chemistry, computer-aided drug design, high throughput screening, and biochemistry.

Aims and objectives

The aim of this project is to capitalise on the group's expertise in the use of the powerful ProTides technology to develop novel small molecule inhibitors of the Hippo signalling pathway.

Technology

The ProTide technology is a prodrug approach developed for the efficient intracellular delivery of nucleoside analogue monophosphates and monophosphonates and has already successfully been used in the development of three FDA-approved drugs including most recently, Remdesivir for COVID-19.

Target

The Hippo signalling pathway plays key roles in organ size control and tumour suppression through the regulation of cell proliferation and apoptosis. Moreover, the regulation of this pathway has a significant impact on patient prognosis and chemotherapeutic drug resistance, hence it has recently become a focal point as a therapeutic target in the treatment of cancer.

More specifically, through an in-house screening of a small library of ProTides, we have recently identified four structurally different ProTides with the ability to modulate this pathway (data unpublished). The project will build on these exciting findings to optimise the structures of the hits into lead compounds with high potency and excellent drug-like properties profiles and then proceed to characterise the lead compounds biochemically and in cells.

Training provided

The prospective student will have access to state-of-the-art laboratories, facilities, and equipment available at the Pharmacy and Life Sciences departments. This multidisciplinary drug discovery project will provide a unique opportunity to receive high-quality training in a range of techniques at the interface of chemistry and biology including computer-assisted drug design, chemical synthesis and analysis (NMR, mass spectrometry, IR and HPLC…etc) as well as cell culture and biochemical based techniques (western blotting, toxicity and biochemical binding assays…etc) for biological evaluation of synthesised compounds. Student will have the opportunity to present his/her research in our weekly lab meetings and will be encouraged to attend and present his/her research findings in national and international meetings. Collectively, the skills to be acquired from working on this project will be extremely valuable for those wishing to pursue a career in academia or with pharmaceutical/biotechnology companies.

First supervisor: Dr Hachemi Kadri h.kadri@kingston.ac.uk

Vision

Explore the coordination behaviour of "accordion-like" multidentate ligand frameworks, identify reactivity patterns with Main Group & Transition Metals to develop new catalytic systems and materials.

Background

We have previously demonstrated that our PE3 ligand skeleton is indeed "flexidentate" and its "accordion-like" flexibility can be used to tune e.g. P-Bi interactions from a weak pnictogen-type through to a formal dative bond (vide infra: publications 1-3). In this PhD project we will extend this idea and perform extensive studies of PE3 ligands with various Main Group and Transition Metal precursors to investigate the interplay between strong and secondary bonding interactions.

Hypothesis and objectives

The combination of both, strong E→M donor bonds and a tunable weak P···M interaction, offers the opportunity to design stable (coordinatively saturated) compounds, which can undergo P···M coordination/de-coordination events. This semi-lability of the ligand allows stabilisation of a compound and at the same time guarantees substrate molecules access to highly reactive metal species. While the stronger ligand-metal bonds provide control over the coordination environment (geometry and sterics), the weak P···M interaction can tune the electronic character of a catalyst without influencing its structure. Furthermore, such secondary interactions may serve as structural anchors in three-dimensional polymeric structures. Therefore, we see an enormous "hidden potential" in this ligand system and believe it will be of high interest for the development of new catalytic systems and materials.

Experimental work

In particular, the PhD student will explore the coordination of the ligand systems to:

a) heavy p-block cations: in particular to InI, SnII, SnIV, PbII and PbIV precursors. Large atom sizes (high coordination number), inert lone pairs and relativistic effects, together with the "flexidenticity" of PS3 & PO3, are expected to deliver distinctive molecular systems (e.g. materials with inorganic-organic perovskite structures. Furthermore, we will use compounds with tuneable, electron deficient SnII and PbII centres (bearing a lone pair) to activate bonds in small molecules (e.g. O2, NH3) or hetero allenes (e.g. CO2 or isocyanates), aiming to develop new, sustainable catalytic systems.

Tin- and lead-containing inorganic-organic hybrid materials exhibit excellent properties as components for various optoelectronic technologies. Thus, we will focus on the characterisation of such new materials (e.g. coordination polymers) and perform extensive photoluminescence studies (collaboration Dr Phil Dyer, Durham University). In the future we aim to employ soluble InI complexes emerging from this work as reducing agents for organic synthesis. Finally, we will test the potential of suitable molecular tin compounds for fluoride ion sensing.

b) Transition Metals: The combination of two quite different soft donor atoms (S and P) in PS3 makes this ligand attractive for coordination studies with soft metal centres (our focus will be on Cu, Au and Pd). Especially PdII, with its preference for square-planar geometries, is expected to deliver unforeseen, possibly polynuclear coordination compounds (building blocks for inorganic polymers). Besides palladium complexes, we will also exploit the potential of new coinage metal complexes of PO3 and PS3 for catalysis. Often, gold compounds react much faster (minutes vs. hours) than catalysts with other transition metals, which can, in principal, catalyse the same reaction (e.g. Pd vs. Au catalysed cyclization reactions). However, this enhanced reactivity can only be achieved with high ligand exchange rates. In this respect, our semi-labile PE3 ligand framework is ideal as it guarantees protection of highly reactive Au centres and at the same time quick clearing of a coordination site for substrate coordination. Finally, the physiochemical properties (photoluminescence) of new copper-containing inorganic-organic hybrid materials (e.g. coordination polymers) will be studied in detail for possible application in optoelectronics.

Computational studies are essential to learn about the reactivity of new compounds. In this context, we will collaborate with the research team of Dr Benko (Budapest University), who specialises in the computation of Transition Metal compounds. In particular, we are interested in the electronic structure of the compounds (HOMO/LUMO, NBO and AIM analyses) to predict their reactivity for possible applications. During the PhD studies the student may spend a few weeks in the group of Dr Benko to learn the basics of DFT calculations. Besides synthetic skills in air-sensitive chemistry and homogeneous catalysis the candidate will acquire a deep knowledge in NMR spectroscopy to characterise compounds and elucidate reaction mechanisms.

First supervisor: Dr Dominikus Heift d.heift@kingston.ac.uk

The permeability of a lipid membrane, such as a cell membrane, relates to the ease with which a chemical entity, such as a drug molecule, can cross the membrane. Inherently, the efficacy of a drug will depend on being able to transverse any membranes encountered during its route to its site of action and hence prediction of permeability is of critical importance. Notably, however, the composition of lipid membranes is diverse and it is therefore plausible to propose that some compounds may be able to pass through certain membranes but not others. Understanding the variation, if any, in permeability of molecules through membranes with respect to the membrane composition itself is imperative.

Various laboratory-based assays, such as the parallel artificial membrane permeability assay (PAMPA) and the Caco-2 cell assay are commonly used to assess the ability of potential drug candidates to pass through membranes, however these can be time-consuming and resource heavy. They also restrict the user to specific membrane compositions albeit that the assays are selected for their relevance; the Caco-2 cell line is a human epithelial cell line commonly used to model the intestinal epithelial barrier whereas the lipid membrane in PAMPA is, typically, not derived from cells but is instead a specific blend of one or more lipids such as dioleoylphosphatidycholine (DOPC) chosen to mimic the lipid composition of the particular membrane of interest, enabling the prediction of permeability measurements due to passive transport only.

The application of computational modelling, such as through membrane dynamics (MD) simulations, to evaluate membrane permeability is increasing. Techniques such as the potential of mean force (PMF) method in MD enable free energy profiles to be generated for the chosen drug, or other molecule, as it traverses across the lipid membrane. However, there is a dearth of research specifically considering the dependence of permeability on the membrane composition, which this project proposes to address.

This PhD student project therefore aims to systematically assess the effect of altering the membrane composition on its permeability to a range of small molecules (< 500 Da) using molecular dynamics simulations. Both coarse-grained and all-atom simulations will be considered, using a molecular dynamics simulation software package such as GROMACS.

First supervisor: Dr Gemma Shearman g.shearman@kingston.ac.uk

Neuronal injury or disease in humans often leads to disability and mortality. Neurons in humans regenerate poorly, and there are very few methods to encourage this regeneration. We are interested in identifying new genetic mechanisms involved in neuronal regeneration. Planaria are an excellent neurobiological model, have many neurotransmitters in common with humans, and have the remarkable ability to regenerate large parts of their nervous system after injury. This PhD project will undertake large-scale gene expression analysis in regenerating planaria head and eye tissue, followed by pharmacological and/or genetic inhibition of novel identified genes in regenerating planaria and cultured mammalian neurons. The objective is to identify novel regeneration-associated genes that may then be investigated further as potential target(s) for regenerative therapies in humans.

The student will gain experience in invertebrate model techniques, mammalian cell culture, RNA-seq and qRT-PCR analysis, protein analysis (Western blotting, immunofluorescence), molecular cloning, and microscopy. The student will join active and supportive research groups, and will be part of the Interdisciplinary Hub for the Study of Health and Age-related conditions (IhSHA) at Kingston University London.

Applicants should have or be expecting to obtain at least an Upper Second (2i) class degree in a related subject (e.g. Biochemistry, Genetics, Biomedical Science). Experience in laboratory work or an MSc/MScR would be an advantage, but training on all techniques will be given.

First supervisor: Dr Francesca Mackenzie f.mackenzie@kingston.ac.uk