Faculty-funded PhD studentships for March 2025 entry

Schistosoma mansoni is one of three major species of schistosome parasites that infect over 240 million people across ~70 developing countries, with an additional 0.6 billion people at risk of infection. These blood-dwelling worms cause the neglected tropical disease human schistosomiasis. The mature adult worms produce hundreds of eggs daily to support disease transmission via snail intermediate hosts. However, many of the eggs don't get excreted and instead become trapped in vital organs, like the liver and spleen, causing damage through tissue inflammation. Adult schistosomes have a typical lifespan of three to five years but can endure for up to two decades in the blood vessels, leading to significant morbidity and mortality in endemic populations.

Control of human schistosomiasis relies heavily on mass drug administration using praziquantel. However, schistosomes may become refractory to this drug. Furthermore, treatment does not prevent re-infection, and some developing schistosome life stages are praziquantel tolerant. Consequently, a deeper understanding of schistosome biology, including that regulating parasite growth and development in the human host, will support future innovative control strategies focused on killing or attenuating the parasite. This project aims to shed light on molecular mechanisms governing the growth and development of the intravascular early stages of the parasite to support future control innovations.

When humans encounter schistosome-infested freshwater, the parasite penetrates the skin and transforms into a skin-stage schistosomulum. It then enters the vasculature, embarking on an extraordinary journey through the lungs (lung-stage schistosomulum) before reaching the hepatic portal vein. Here, it develops into the liver-stage

schistosomulum, which grows rapidly and develops into morphologically distinct male and female adult worms, which pair up and produce eggs. Despite the importance of the liver stage schistosomulum, existing research has predominantly focused on adult schistosomes, leaving a significant gap in our understanding of the molecular control of growth and development of this critical life stage.

We will grow schistosomula to the liver stage, in vitro, using our existing approaches. These will then be used to answer important questions in schistosome developmental biology. Such questions will include:

1. What is the molecular nature of the liver schistosomulum tegument (surface layer);
2. To what extent do host molecules such as human growth factors interact with the tegument and drive liver somule growth and development?
3. What are some of the key regulators of somatic stem cell (neoblast) proliferation in the liver schistosomulum?
4. Do liver schistosomulum communicate with the adult schistosomes that inhabit a different niche to support their development. There is significant scope in the project for exploratory research, including beyond these questions.

We invite talented and motivated researchers interested in cell biology to join us. This project offers comprehensive training in molecular parasitology, encompassing various approaches including bioinformatics, proteomic-based techniques, confocal laser scanning microscopy, stem cell analysis, drug assay development, and phenotype assays.

Applicants should have achieved at least an Upper Second (2i) class degree in a related subject (e.g. Biochemistry, Genetics, Biological Sciences). Experience in laboratory work or an MSc/MSc by Research would be an advantage.

First supervisor: Dr Eman Shakir

Candidates are invited to join the Kadri Lab, where our research focuses on developing innovative chemical approaches for discovering novel therapeutics to address unmet global health needs. Our research is multidisciplinary, spanning the fields of chemical biology, medicinal chemistry, computer-aided drug design, high-throughput screening, protein crystallography, and biochemistry.

This project will build upon our recent exciting findings in deciphering the important role of the Hippo signalling pathway and its implications in various health diseases, particularly cancer. The Hippo pathway is emerging as a potential target for cancer immunotherapy. Modulating the pathway's activity may enhance the effectiveness of immunotherapies by promoting immune recognition and activation against cancer cells. The aim is to capitalise on the group's expertise in the use of structure-based drug design and the powerful PROteolysis Targeting Chimera (PROTAC) technology to develop novel small molecule modulators of this pathway.

The candidate will have access to state-of-the-art laboratories, facilities, and equipment available at Kingston University London. This multidisciplinary drug discovery project will provide an excellent 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, targeted protein degradation, cell culture, and biochemical-based techniques for the biological evaluation of the synthesized compounds.

First Supervisor: Hachemi Kadri

Post-surgical wound care often presents complex challenges, including the need for efficient wound healing and effective pain management. Traditional therapeutic approaches typically focus on either wound healing or pain relief separately, which can lead to non-ideal patient outcomes. This research aims to explore the design and application of hybrid nanocarriers capable of delivering both therapeutic effects simultaneously: accelerating wound healing and providing controlled and localised analgesic effects.

The primary goal of this project is to develop hybrid nanocarriers that can encapsulate and co-deliver active pharmaceutical ingredients (APIs) for both wound repair and pain relief agents. These nanocarriers will be optimised for controlled release, biocompatibility, and targeted delivery, ensuring their effectiveness and safety in the complex microenvironment of post-surgical wounds.

This is an interdisciplinary project which combines nanotechnology, pharmaceutical sciences, and biomedical engineering to solve real-world challenges in patient care. The candidate will explore novel hybrid nanocarrier designs, focusing on enhancing their controlled therapeutic efficacy while minimising potential side effects. They will also evaluate and characterise the performance of these nanocarriers in vitro and ex- vivo, assessing their impact on wound healing and pain management.

The ideal candidate should have at least a 2:1 Honours degree (or equivalent) in Pharmaceutical Sciences, Pharmacy, Materials Science, or a related field. A relevant masters degree and/or experience in nanotechnology or drug delivery systems will be an advantage. Strong laboratory and analytical skills in drug formulation, characterisation, and cell culture are desirable. Experience with cell-based models, as well as proficiency in data analysis and scientific writing, will be beneficial.

First Supervisor – Dr Ruba Bnyan

Child Observation is a central and valuable tool in the fields of children's social work, child psychology and psychiatry. Professionals often observe the interactions between a child and their parent or caregiver, applying relevant theory to reach conclusions about the nature of their relationship and the child's attachment style. In more acute cases where a child is believed to have suffered, or be at risk of suffering, significant harm due to their caregiver's behaviour, child observation can play a critical role in professional assessments, including their assessment of whether the caregiver should be allowed to care for the child. A common setting for these observations is in a children's contact centre, where contact between a parent and a child takes place after a child has been removed into care, with a supervisor present throughout. The supervision role fulfils two functions: to ensure the child's safety; and to provide observations to guide professional assessment.

This project will interrogate the validity of this observation model as a tool for drawing conclusions in the family court. While professionals draw on their skill as observers, and on a wealth of research evidence, they are also prone to ‘heuristics' – the mental shortcuts that leave all of us at risk of unconscious bias. This project will test the role played by social psychological heuristics in observations of contact between a parent and child. The findings will be instructive for professionals' own development and reflection, and for the family courts who regularly hear evidence based on child observation. The findings of this study could, critically, have a bearing on how evidence is weighed in highly sensitive child care proceedings.

The PhD candidate should have a background in qualitative methods and skills in developing creative research designs. Experience in some form of children's work (e.g. social work or psychology) is an advantage.

The deadline for applications is 20 January with interviews conducted in mid-February. Applicants are asked to submit their CV and certificates, including English language at an acceptable (see University website) level. References will be taken up before interview. The expected start date of the project is March 2025. Please apply via the Kingston University website, ensuring that you apply for March 2025 entry and state that you are applying for a studentship for this project in your application documents.

First supervisor: Chris Dyke

This PhD project will be a unique sub-study of the DAPPLE project, a 3-year NIHR-funded study aimed at developing effective service models for providing palliative and end of life care (PEOLC) for people with a learning disability (see www.dappleproject.com).

 There are around one million people with a learning disability in England. People with a learning disability die on average 22 years earlier than the general population. They face stark health and mortality inequalities, including inequal access to PEOLC services. Challenges include difficulties with communication which affect all aspects of palliative care provision, including pain and symptom assessment; lack of involvement in end-of-life decision-making; multi-morbidity and polypharmacy; complex social circumstances involving families as well as care staff; lack of reasonable adjustments to care; and lack of experience among learning disability staff of illness, death and dying, leading to fear and avoidance. Staff providing PEOLC to people with a learning disability also have significant training needs.

The DAPPLE project will explore, compare, and contrast PEOLC services for people with a learning disability in four geographical areas (Study Sites) in England. Part of the methodology within those localities is to conduct case studies of people with a learning disability currently approaching end of life (n=up to 20), using ethnographic methods; and retrospective case reviews of people with a learning disability who have died, using interviews with key family/carer/staff. The project aims to identify the barriers and enablers to providing accessible, high quality PEOLC to people with a learning disability, and the replicable elements of good practice.

This PhD project is a sub-study of the DAPPLE project focusing on the perspectives of paid care staff of people with a learning disability who are approaching the end of life. The majority of people with a learning disability who die in England live in a residential care setting at the time of death, supported by learning disability service providers. Staff working within these services are therefore at the forefront of supporting people with a learning disability at the end of life. However, there is consistent evidence that they lack expertise, skills, knowledge and confidence in this area.

The DAPPLE project will collect data from people with a learning disability at the end of life, mostly through observation but also through interviews with the main family member or carer(s). Participants in the retrospective case studies similarly consist of the main carer(s). This PhD project will focus on learning disability support staff who have been involved in supporting a person within the DAPPLE case studies who is terminally ill or who died, but who were not the key carer or key staff. Day-to-day support is often provided by a wider team of staff that may include part-time workers and agency staff, whose perspectives and support needs have not been a focus for investigation. It is also not clear how the level of expertise, skills and confidence of learning disability support staff impacts on the support provided to people with a learning disability at the end of life.

The PhD project will explore the experiences and views of these staff members, as well as the impact of their caring role on the experience and outcomes for the person at the end of life whom they support. A range of data collection methods may be considered; this may include (but is not limited to) interviews, focus groups, observation and/or questionnaires. The specific research questions and appropriate methodology will be agreed upon by the students and the supervisory team. It is anticipated that data will be collected within one or more of the four DAPPLE study sites (Croydon, Milton Keynes, Leicester, Kirklees).

First Supervisor: Andrea Bruun

The valorisation of glycerol has gained significant recent attention as it is considered as an industrial waste product from biodiesel production. It is well-documented that the worldwide production of biodiesel (25 bn L/yr.) entails an enormous generation of glycerol, and Colombia especially, with its immense biofuel industry (110000 barrels per day), contributes a significant amount. Thus, the development of efficient and sustainable chemical processes for the conversion of glycerol into valuable chemical products is of great interest.

The proposed project will focus on the synthesis of catalysts for dehydrogenation reactions to convert glycerol into dihydroxyacetone, which is an important raw material for cosmetic products. Furthermore, this process generates hydrogen gas, which can either be used as fuel or be recycled in other chemical processes (e.g. hydrogenation reactions).

Our preliminary studies show that ruthenium-based catalysts exhibit high activity and exceptional selectivity (compared to e.g. iron compounds) for the controlled dehydrogonation of glycerol. Due to their unique stereo-electronical properties, N-Heterocyclic Carbene (NHC) ligands are versatile ancillary molecules, which form robust NHC–metal bonds that may enhance the catalytic activity of the ruthenium metal centre. Surprisingly, such NHC-ruthenium systems are under-explored as catalysts for glycerol valorisation processes.

In collaboration with the research group of Dr Baquero (National University of Colombia) the new NHC-Ru complexes will be extensively tested as catalysts in high pressure autoclave reactors for homogeneous dehydrogenation reactions of glycerol. Depending on the solubility and the stability of the catalyst (tuned by functional groups in the NHC ligand framework), these reactions will be carried out in organic solvents or, to develop more sustainable processes, in water.

Solid supports may provide high stability and enhanced reactivity to molecular catalysts upon chemical immobilisation. Colombian clays are earth-abundant, non-toxic, and low-cost natural minerals, which are mainly composed of SiO2, Al2O3 and Fe2O3. Due to their layered structure, these materials have a large adsorption capacity and are thus ideal heterogeneous supports for molecular catalysts. The student will explore chemical deposition of the synthesised NHC–Ru complexes onto Colombian clays, to achieve heterogeneous-supported Ru-based catalysts. These composites with expected enhanced catalytic activity will be systematically characterised and then tested for heterogeneously catalysed dehydrogenation reactions of glycerol.

Objectives:

• Synthesis and characterisation of NHC–Ru(II) complexes.
• Deposition of NHC-Ru compounds onto Colombian clays.
• Catalytic dehydrogenation of glycerol with Ru complexes and Ru-clay composites.
• Synthesis of NHC ligands

Adapting literature procedures, the student will prepare NHC ligand systems with sterically hindered moieties and appropriate substituents to achieve lipophilicity (aromatic groups) or hydrophilicity (sulfonate groups), respectively. Importantly, these ligand frameworks will contain a hydroxyl moiety, to facilitate chemical deposition onto the clay support. The new NHC ligands will be characterized by conventional analytical techniques (NMR, EA, MS, etc.).

Synthesis of NHC–Ru(II) complexes

The NHC-Ru complexes will be synthesised following the in situ free-carbene approach: The NHC precursors (imidazolium salts) are reacted with a base and converted to the free NHC ligands, which are subsequently reacted with a Ru precursor. The new complexes will be purified and characterised by conventional analytical techniques (NMR, EA, MS, XRD).

Deposition of NHC–Ru(II) complexes onto Colombian clays

To achieve the chemical deposition of NHC-Ru complexes on a substrate, the clay will be activated following an established delamination process. This superficial exfoliation of the mineral results in an increased surface area. Subsequently, condensation reactions (between Lewis Acid sites on the clay and hydroxyl groups in the Ru complex backbone) allow the immobilisation of the catalysts on the clay surface. These Ru-clay composites will be characterized by SEM, EDX, N2 adsorption-desorption isotherms analysis, ICP, powder XRD, TGA. Furthermore, the project will benefit enormously from KU's new solid-state NMR facilities to characterize the catalyst material in the solid state.

Catalytic tests: Dehydrogenation of glycerol (NUC)

Both, Ru complexes and Ru-clay materials will finally be tested for the catalytic dehydrogenation of glycerol. For this part of the project, we will collaborate intensely with Dr Baquero and his team, as they have profound experience in the catalytic transformation/valorisation of natural products. All reactions will be monitored by GC-MS and NMR spectroscopy to detect the formation of dihydroxyacetone and molecular hydrogen. Recyclability of the materials will be assessed to study catalyst stability and activity.

First Supervisor – Dr Dominikus Heift

Muscle contraction of the heart pumps blood around the body and skeletal muscle contraction enables body movement. Muscles can be divided into two groups, striated muscles which include cardiac and skeletal muscles, and non-striated smooth muscles. The M-band is a central component of the contractile unit (sarcomere) of striated muscles but is the least studied. The M-band plays an essential role in muscle function and in controlling the heart rate. Published reports link M-band proteins and cardiac disease. The proposed research aims to understand the atomic details of the M-band and therefore shed light on molecular mechanisms underlying M-band function.

The proposed PhD project is a collaborative project between Dr Katya Lamber (Kingston University London) and Dr Pinotsis (Institute of Structural and Molecular Biology, UCL and Birkbeck College).

Students will learn a variety of techniques including cloning, protein expression and purification, protein crystallization and protein structure determination by X-ray crystallography, basic cell biology techniques and activity assays.

This is an exciting opportunity for a talented and motivated prospective PhD candidate with a passion for structural biology and biophysics. We are looking for an enthusiastic candidate with BSc/MSc in a relevant biological subject, independence and initiative are essential, MSc is desirable.

First Supervisor – Dr Katya Lamber