2025 Summer Projects

Investigating Inflammation in colon pre-cancerous conditions across colon segments

Supervisor: Francesco Boccellato

Location: Ludwig Institute for Cancer Research, Oxford

Colorectal cancers arise from benign polyps, which have the potential to develop into aggressive malignant tumors in both women and men. Two distinct molecular pathways contribute to the formation of these polyps:

Conventional adenoma-carcinoma pathway (~70%) – This pathway typically involves stepwise genetic alterations, leading to the progression of adenomatous polyps into colorectal cancer.

Serrated neoplasia pathway (~30%) – This pathway gives rise to sessile serrated lesions (SSLs), which are more frequently found in the proximal colon but can also develop in the distal colon.

Project Scope

We have acquired biopsies from sessile serrated lesions and adenomas located in different segments of the colon. The aim of this project is to determine the expression levels of pro-inflammatory genes in these distinct lesions to assess whether inflammation is equally present across all colon segments. Understanding the inflammatory landscape of sessile serrated lesions may provide insights into their potential for malignant transformation and regional differences in tumorigenesis.

Skills and Techniques

During this project, the student will gain hands-on experience in:

-Nucleic acid extraction from tissue samples

-Primer design for gene expression analysis

-Real-time quantitative PCR (qPCR) to quantify inflammation-related gene expression

This project offers an excellent opportunity to develop expertise in molecular biology techniques while contributing to our understanding of inflammation in colorectal tumorigenesis.

RNA Pseudouridylation in cancer

Supervisor: Chunxiao Song

Location: NDM Research Building, Oxford

Cellular RNA is decorated with diverse chemical modifications, which participate in all aspects of RNA biology. The multitude of modifications in RNA adds a new layer to gene regulation, leading to the emerging field of epitranscriptomics. Our research aims to decode the chemical modifications of our genome, transcriptome, and proteome in human health and disease – cancer in particular – and translate this information into diagnostic and therapeutic opportunities that ultimately benefit patients.

Recently, we developed a novel sequencing method, called BACS, for the most abundant RNA modification pseudouridine (Nat. Methods 2024, https://doi.org/10.1038/s41592-024-02439-8). We are now studying the role of pseudouridine and pseudouridine synthases (PUS) in cancer, and exploring the potential clinical application.

The Global Health Network: Strengthening research capacity in low-resource healthcare settings through building regional networks, coordination of training and knowledge sharing activities and measuring impact of the initiatives implemented

Supervisor: Adam Dale

Location: Ewert House, Summertown, Oxford

The Global Health Network (TGHN) is a facility that works across all aspects of health research with the objective of embedding health research where evidence is lacking by bringing support, training and resources for faster and higher-quality research processes. This is achieved through an online platform for knowledge sharing, strategic partnerships, and training and career development for research teams and individuals. TGHN has adopted a model of federated and regional leadership in which partner research institutes in Africa, Asia, Latin America & Caribbean and Middle East & North Africa lead the organisation and delivery of context-relevant research training and capacity strengthening initiatives.

The student will undertake activities within the regional programmes including: digital content management, implementing communication strategies, drafting of manuscripts, developing frameworks for and measuring impact of the activities implemented, document preparation (reports, collaboration agreements), mapping resources relevant to the knowledge communities across all four regions, with a particular focus on projects related to Environmental Surveillance, AMR and Artificial Intelligence in Global Health.

ODIN

Supervisors:  Adam Dale and Paul Kingpriest

Location: Ewert House, Summertown, Oxford

The ODIN consortium behind the project is a collaborative research and capacity building effort bringing together a diverse group of leading institutions from around the world that aims to establish innovative and adaptable infectious disease surveillance in sub-Saharan Africa.

Strengthening Environmental Surveillance to Advance Public Health Action – Wastewater Surveillance Project , Countries involved: Burkina Faso, DRC and Tanzania.

https://odin-wsp.tghn.org/

Responsibilities/Objectives

· Devise and deliver an overall project action plan for enhancing research capacity and Knowledge Sharing across the three participating African countries

· Support colleagues in developing and using systems, processes and frameworks for reporting activities and tracking the impact of our work

· Contribute to ODIN-related papers and conference attendances where necessary

· Organise and coordinate activities within the workplan, such as: context analysis, webinars and workshops, with the potential for seminars, meetings and webinars, sharing of resources, supported learning sessions and working groups

· Contribute to the development of new resources for the project

· Attend training with our in-house digital team on how to use the content management system and project management systems

· Contribute to the upload of resources into the ODIN page and news items into the social media platforms.

· Track activities and evaluate achievement of milestones and deliverables.

Preferred Candidate Profile

Core Skills and Competences

Ability to be flexible and work across several projects drawing from a range of skills including communication skills, organisational abilities and strong interest in developing a web-based resource for learning and knowledge sharing.

Other important considerations

Experience with social media and websites useful but not essential.

1000 challenge

Supervisors:  Adam Dale and Paul Kingpriest

Location: Ewert House, Summertown, Oxford

A bold new initiative being rolled out across the world by The Global Health Network and Nursing Now to enable 1000 nurses, midwives, community health workers and other allied health professionals in low-resource settings to lead pragmatic health research studies that gather evidence to address priority issues in their communities while developing skills and leadership experience - https://1000challenge.tghn.org/

Responsibilities/Objectives

1. Project management including; oversight, driving uptake, troubleshooting and supporting teams with the use of the online platform

2. Foster a collaborative and supportive environment for participants, encouraging skill development and leadership experience

3. Contribute to the development or highlighting of resources and training materials to enhance the research capabilities of participants

Preferred Candidate Profile

Core Skills and Competences

Ability to be flexible and work across several projects drawing from a range of skills including communication, problem-solving and project management.

Interest in health research capacity building and building communities of practice.

Synthetic Data Generation: Disease-Agnostic and Disease-Specific Approaches

Supervisors: Estaban Garcia-Gallo and Tom Edinburgh

Location: Big Data Institute, Oxford

This project aims to develop synthetic data generation models that can either be disease-agnostic or disease-specific. Initially, COVID-19 data may be used for training, with potential retraining on other datasets. The project will also evaluate synthetic data quality, balancing privacy and fidelity concerns, and propose methods for assessing the utility of synthetic data in epidemiological and clinical research.

Structural analysis of ATRX for the development of PROTAC degraders against childhood solid tumours

Supervisors: Lizbé Koekemoer, Cassandra Adams and George Randall

Location: Centre for Medicines Discovery (CMD), Oxford

Neuroblastoma is both the most common solid tumour of young children and a leading cause of death from treatment-refractory cancer relapse in all children. It is one of several “transcriptionally addicted” cancers dependent on abnormally high-level expression of transcription-factors or fusion proteins, in this case N-Myc protein caused by amplification of the MYCN proto-oncogene. Our overall goal is to development a therapeutic that uses the exciting degrader (“kiss-of-death”) approach to eliminate a support protein (ATRX) that is key to the oncogenic activity of MYCN, using heterobifunctional molecular glues and PROTACs that trigger specific elimination of ATRX.

In the primary stages of the project we propose to thoroughly map the binding opportunities across ATRX using crystallographic fragment screening. To do this, we first need to establish a robust crystal system that can be used in these experiments. In this internship we want to (1) do bio-informatic analysis of ATRX to determine the ideal boundaries for crystallography, (2) protein production of the ATRX protein and (3) establishing robust crystal systems for ARTX.

Testing of Question Formats in Case Report Forms

Supervisors: Estaban Garcia-Gallo and Sara Duque Vallejo

Location: Big Data Institute, Oxford

This project will use A/B testing to evaluate how different ways of structuring questions in Clinical Characterization Case Report Forms (CRFs) impact data capture time and the reliability of the collected evidence. The study will test variations in question formats (e.g., open-ended vs categorical, dropdowns vs checkboxes, default options vs mandatory fields) to determine their effects on data completeness, response consistency, and usability.

Health Workforce Unemployment and Underemployment in the UK and Europe

Supervisor: Yingxi Zhao

Location: Peter Medawar Building (PMB), Oxford

Health systems depend on a well-functioning workforce, yet recent surveys and analyses reveal a growing issue of unemployment and underemployment among healthcare workers in both high- and low-income countries. For example, a British Medical Association (BMA) survey found that many general practitioners in England are considering leaving the NHS because of limited employment opportunities.

The HSC research team has been studying different workforce challenges, including how health service redesign interacts with workforce planning. Building on this ongoing research, this summer studentship project will involve conducting a systematic review of academic literature and a document review of major media outlets to explore health workforce unemployment and underemployment. The focus will be on key professional groups, including medical doctors, nurses, and midwives.

We are seeking students interested in health systems and human resources for health. The successful candidate will help screen and synthesise data and contribute to reporting the findings. This will include presenting results at internal research group seminars and, where relevant, sharing insights with external stakeholders such as the General Medical Council, Nursing and Midwifery Council, BMA, and relevant Royal Colleges.

Structural enablement of a novel, broad-spectrum antimicrobial target

Supervisors: Annette von Delft, Lizbe Koekemoer and Lenye Dlamini

Location: Centre for Medicines Discovery (CMD), Oxford

Antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of infections and the existing antimicrobial pipeline does not match the scale of the global health problem which claims over 2 million lives a year.  This is particularly relevant for a group of six highly virulent and resistant bacterial pathogens known as the ESKAPEE group (E.faecium, S.aureus, K.pneumoniae, Acinetobacter spp., P.aeruginosa, Enterobacter spp., E.coli). It therefore remains an urgent priority to discover novel classes of antibacterial compounds that act by different molecular mechanisms than existing antibiotics.

UMP kinase is a target that would be fit for this purpose. This enzyme is required for de novo pyrimidine biosynthesis and is essential for bacterial growth and energy metabolism. It is highly conserved between bacteria with the opportunity to develop broad spectrum antimicrobials, and don’t have a eukaryotic homologue (eukaryotes have a single bifunctional (UMP/CMP kinase). Further, biochemical assays are readily available and multiple structures have been deposited to the Protein Data Bank.

In this project we want to study the UMP kinase enzymes from the various ESKAPEE enzymes. This include (1) bio-informatic analysis of the proteins, (2) cloning, (3) enzyme production and (4) establishing crystal systems. If the project progresses well the scope can be expanded to include a crystallographic fragment screen using the XChem facility at Diamond light source.

Lived experiences of climate change and health in Indonesia, Nepal, and Vietnam

Supervisors: Sonia Lewycka, Hai Ngo and Tess Johnson

Location: Oxford at the Ethox Centre

Climate change is the single biggest health threat facing humanity, and health featured highly on the agenda at COP 28 in Dubai. Extreme weather events may have direct effects on health, such as through heat stress, air quality, water quality and quantity, food security and safety, and vector distribution and ecology. Many infectious diseases are highly sensitive to climate conditions, and climate change can lead to increased prevalence, geographical spread and longer transmission seasons. Climate change also has impacts on food and water security, through floods and drought, leading to malnutrition and undernutrition. Fossil fuel combustion contributes to greenhouse gases as well as to high levels of air pollution. Air pollution is estimated to account for 7 million premature deaths per year, and cause one in nine deaths worldwide.

Climate change may also undermine many of the social determinants for good health, such as livelihoods, equality and access to health care and social support structures. These climate-sensitive health risks are disproportionately felt by the most vulnerable and disadvantaged, including women, children, ethnic minorities, poor communities, migrants or displaced persons, older populations, and those with underlying health conditions. All of these factors may impact health system capacity and resilience.

We have interviewed people living in climate affected communities across 12 locations in Indonesia, Nepal, and Vietnam to explore their lived experiences of changing climates, their perceptions of how this is affecting their health, wellbeing, and livelihoods, and what actions they are taking. Photo stories have also been gathered to illustrate the impacts of climate change on health. This project would entail qualitative analysis of interviews and photos.