Department of Oncology and Metabolism projects

Intercalated BSc Medical Sciences Research available projects

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Projects: 

Rare disease phenotyping and genotype-phenotype correlation

Main Supervisor

Dr Meena Balasubramanian (m.balasubramanian@sheffield.ac.uk)

Second Supervisor

Professor Nick Bishop (n.j.bishop@sheffield.ac.uk)

Aim and Objectives

Phenotyping of patients with rare genetic disorders including Osteogenesis Imperfecta
Generating unique methylation episignature for OI and other rare genetic disorders
Understanding better the developmental profile of rare forms of OI

Overarching research question:
Assessing developmental profile in children with heritable bone fragility disorders such as Osteogenesis Imperfecta: is intellectual disability part of the phenotype?

Research Methodology

Clinical phenotyping;
Data collation from clinical records
Developmental assessment and co-ordination
DNA samples for methylation episignature
Patient consent
Writing up case series of patients with rare genetic disorders

Expected Outcome

Clinical series in a peer-reviewed journal
Methylation episignature for OI
Conference abstracts

Type of Project

Clinical project - based in the clinical environment with patients/including service evaluation

Additional Training

Variant interpretation; clinical phenotyping; lab work if interested

Study of Pressure Sensing Insoles in Diabetic Foot Ulcer Recovery (STRIDER)

Main Supervisor

Dr Dinesh Selvarajah (d.selvarajah@sheffield.ac.uk)

Second Supervisor

Professor Solomon Tesfaye (solomon.tesfaye@nhs.net)

Aim and Objectives

One in four patients with diabetes will develop a foot ulcer and one in five patients with a foot ulcer requires an amputation. This is devastating for the patient and their family. It is also costly for the NHS. Over £119 million is spent each year in England on diabetes-related amputations. The numbers of amputations are rising and urgent action is needed to reverse this trend.
The lynchpin of foot ulcer care is pressure off-loading. The aim of this study is to examine if the use of smart-insoles, which provides real-time feedback of in-shoe foot pressure will accelerate the wound healing process in patients with diabetic foot ulcers.

Research Methodology

We are conducting a 12-week, open labelled study over 6 months. Twenty participants will attend six fortnightly visits to coincide with existing clinic appointments. All patients will receive the FEETME Smart Insoles system fitted in a DH walker. Smartphone application alerts (visual, tactile and audible) will notify users when foot pressure exceeds safe limits. Participants will be asked to walk a few steps or simply lift their foot up until the alert is turned off. At each study visit a photograph of the ulcer will be taken. The area will be measured using the ImageJ software. Ulcer healing is defined as complete wound skin closure which is maintained for 4 weeks.

Expected Outcome

You will be working with our research podiatrists on this study helping with recruiting study participants, performing study assessments at each visit, collating and analysing study data.

Type of Project

MSc course

Additional Training

The research training you will be provided during this BSc will be sufficient to complete this project.

How and why does our brain age? Using zebrafish as a model to decipher the role of telomerase, DNA damage and senescence in the ageing brain

Main Supervisor

Dr Catarina Henriques (c.m.henriques@sheffield.ac.uk)

Second Supervisor

Miss Pamela Ellis (p.s.ellis@sheffield.ac.uk)

Aim and Objectives

Brain ageing and related neurodegenerative diseases have dramatic consequences in quality life as well as medical care costs in elderly and, therefore, it is urgent to understand the mechanisms underlying it. Decreased telomerase expression, telomere shortening and senescence-associated markers have all been independently observed in the ageing brain and associated with disease. Senescence cells are non-proliferative but metabolically active, realising several factors that can damage surrounding tissue. Importantly, accumulation of senescent cells has been associated with several age-related diseases. However, causality between limited telomerase expression and increased DNA damage and cellular senescence in the natural ageing setting is yet to be established.
This qualitative project aims at establishing whether there is a telomerase-dependent increase in DNA damage and senescence in the ageing brain. We use zebrafish as a model, since it shares many ageing features with humans. This project is part of ongoing work in the lab and it will provide key data for a publication and future grant applications, aiming at identifying therapeutic strategies to prevent or delay age-associated neurodegeneration and disease in the brain.

Objective 1: Quantify DNA damage and senescence markers in the aged Zebrafish brain in the presence and absence of telomerase (yh2ax, p16, p21)

Objective 2: Quantify neurogenesis in the aged zebrafish brain in the presence and absence of telomerase, and determine whether stem cells become senescent with ageing (Edu/S100/p16)
 

Research Methodology

The student will be performing image processing and quantification of specific immunofluorescence staining in zebrafish brain sections. The images are ready to quantify. The student will be taught to use ImageJ, Excel, GraphPad prism and Illustrator to process, analyse, quantify and present data in the form of figures suitable for publication.

Expected Outcome

Outcome should be a figure/s with multiple panels, with associated significant quantification/analysis of results of DNA damage, neurogenesis and senescence at a level suitable for publication. If successful, the student will be an author in the publication we aim to submit in 2022/23.

Type of Project

Qualitative Project/non-lab based - primarily using qualitative methods

Additional Training

The student will be taught to use ImageJ, Excel, GraphPad prism and Illustrator to process, analyse, quantify and present data in the form of figures suitable for publication. Basic statistical training will also be provided, as well as general scientific thinking, hypothesis testing and immunofluorescence analysis. The student will also get a basic training on the anatomy of the brain and specific cellular and molecular mechanisms of ageing.
 

How and why does our brain age? Using zebrafish as a model to decipher the interplay between senescence and inflammation in the ageing brain and the potential role of telomerase

Main Supervisor

Dr Catarina Henriques (c.m.henriques@sheffield.ac.uk)

Second Supervisor

Miss Pamela Ellis (p.s.ellis@sheffield.ac.uk)

Aim and Objectives

Brain ageing and related neurodegenerative diseases have dramatic consequences in quality life as well as medical care costs in elderly and, therefore, it is urgent to understand the mechanisms underlying it. Decreased telomerase expression, senescence-associated markers and inflammation have all been independently observed in the ageing brain and associated with disease. Senescence cells are non-proliferative but metabolically active, realising several factors, including pro-inflammatory molecules, that can damage and promote inflammation in the surrounding tissue. Importantly, accumulation of senescent cells has been associated with several age-related diseases. However, causality between limited telomerase expression and increased senescence in the natural ageing setting, and whether these drive neuroinflammation is yet to be established.
This qualitative project aims at establishing whether there is a telomerase-dependent increase in senescence and inflammation in the ageing brain. We use zebrafish as a model, since it shares many ageing features with humans. This project is part of ongoing work in the lab and it will provide key data for a publication and future grant applications, aiming at identifying therapeutic strategies to prevent or ameliorate ageing and age-associated neurodegeneration and disease in the brain.

Objective 1: Quantify levels of inflammation in the aged Zebrafish brain in the presence and absence of telomerase, using zebrafish transgenics and L-plastin (pan-immune marker) staining)

Objective 2: Quantify senescence (Senescence-Associated-β-gal staining) in the aged zebrafish brain in the presence and absence of telomerase.

Research Methodology

The student will be performing image processing and quantification of specific immunofluorescence staining in zebrafish brain sections. The images are ready to quantify. The student will be taught to use ImageJ, Excel, GraphPad prism and Illustrator to process, analyse, quantify and present data in the form of figures suitable for publication.

Expected Outcome

Outcome should be a figure with multiple panels, with associated significant quantification/analysis of results of inflammation (number of immune cells) and senescence (Senescence-Associated-β-gal staining) at a level suitable for publication. If successful, the student will be an author in the publication we aim to submit in 2022/23.

Type of Project

Qualitative Project/non-lab based - primarily using qualitative methods

Additional Training

The student will be taught to use ImageJ, Excel, GraphPad prism and Illustrator to process, analyse, quantify and present data in the form of figures suitable for publication. Basic statistical training will also be provided, as well as general scientific thinking, hypothesis testing and immunofluorescence analysis. The student will also get a basic training on the anatomy of the brain and specific cellular and molecular mechanisms of ageing.

Real-world data from the I-CAH Registry on the care provision of patients with congenital adrenal hyperplasia in the United Kingdom

Main Supervisor

Dr Nils Krone (n.krone@sheffield.ac.uk)

Second Supervisor

Dr Irina Bacila (i.bacila@sheffield.ac.uk)

Third Supervisor

Dr Neil Lawrence

Aim and Objectives

In the United Kingdom, around 70 children are diagnosed with congenital adrenal hyperplasia (CAH) every year. Patients present cortisol and mineralocorticoid deficiency, as well as hyperandrogenism, requiring life-long hormone replacement therapy. The management of children with CAH is challenging, as they require relatively high doses of glucocorticoids to normalise adrenal androgen excess. Many patients develop multiple co-morbidities, including growth problems in childhood, metabolic and cardiovascular disease, as well as reduced quality of life. In a recent study, we found wide variations in the management used by different countries when treating CAH in children, however, data from the UK was limited. We estimate that the approach to hormone replacement therapy and monitoring is likely to have an impact on patient outcomes and quality of life, thus, an overview of current practice of the management of CAH will help improve the quality of care.

The study aims to explore the ongoing clinical practice and care provision for patients with CAH at a national level. We will collaborate with the I-CAH/DSD registry (https://home.i-cah.org) which provides an already well-established platform for data collection, used by clinicians world-wide to regularly record data on patients with CAH.

The primary objective is to identify trends in the hormone replacement therapy with regards to medication used, number and timing of administrations, doses of gluco- and mineralocorticoids. The secondary objective is to explore variations among clinicians/centres in the strategies used to provide and monitor replacement therapy in CAH (type, administration regime, doses, clinical and biochemical markers of control) and their impact on health outcomes (growth, weight gain, cardiovascular disease, metabolic syndrome).

The overarching research question: Are there significant differences in the administration of hormone replacement therapy in CAH among various UK centres and do they influence heath outcomes?

The project hypothesis: Better understanding of the interrelation between management strategies and health outcomes will help develop a standardised approach to therapy and reduce mortality and morbidity in CAH.

Research Methodology

Clinical data recorded regularly by UK clinicians will be collected from the I-CAH registry, both retrospectively (over the last five years) and prospectively (on annual basis) and analysed to meet the objectives.

The student will participate in data collection (recording in the registry data from patients under follow up at Sheffield Children’s Hospital) and data analysis. They will have the opportunity to experience working with real-world data, using an international platform for data collection. They will develop their skills in medical statistics and their aptitudes in using statistics and graphics software, including SPSS, R, GraphPad Prism and Adobe Illustrator.

Expected Outcome

We expect that this project will provide an overview of the current UK practice of the management of CAH in patients under 18 years of age, allowing to identify differences in the treatment and monitoring strategies used by different centres. This in turn will help explore the efficacy of certain management approaches in relation to patient outcomes and ultimately help improve patient care nationwide. We intend to disseminate our findings in the I-CAH/DSD newsletter, as well as through presentations at national and international meetings and journal publications.

Type of Project

Clinical project - based in the clinical environment with patients/including service evaluation

Additional Training

The student will conduct the project within an experienced team of clinical researchers. They will be encouraged to participate to endocrine outpatient clinics and to the regular departmental educational meetings. They will have weekly meetings with their supervisors to monitor their progress and address potential problems. Additional support will be provided by the supervisors to help develop their skills in statistics and using statistical and graphic software, in the form of one-to-one tutorials or guidance towards free online learning material.

Lung MRI for Risk Stratification to select non-small cell lung cancer patients for radical treatment (LUMRIS)

Main Supervisor

Dr Bilal Tahir (b.tahir@sheffield.ac.uk)

Second Supervisor

Professor Matthew Hatton (matthewhatton@nhs.net)

Third Supervisor

Professor Jim Wild

Aim and Objectives

The objective of this study is to clinically evaluate the feasibility of introducing advanced functional MRI techniques into the current lung cancer diagnostic pathways across a cancer network and to assess its impact on multi-disciplinary team (MDT) decision-making for risk stratification of non-small cell lung cancer patients.

Primary Objective
To assess the feasibility of adding functional lung MRI to the diagnostic MDT pathways for radically treatable lung cancer.

Secondary Objectives

1. To assess the impact of introducing this technology on MDT decision-making for risk stratification.
2. To assess the accuracy of functional MRI for predicting post-treatment lung function measurements.
3. To investigate if functional MRI can detect early and late post-treatment changes in lung function.
4. To develop a robust and repeatable functional and structural lung MRI protocol that can be implemented on any MRI scanner in the region.

Research Methodology

The student will be responsible for the following:
- Applying image analysis techniques, including lung segmentation. This includes developing robust pipelines for image and data analysis techniques.
- Providing patient support and being present at patient imaging procedures. They will also be involved in administrating Xenon gas to the patient and coach the patient in performing breathing manoeuvres required for imaging.
- Assisting with integrating images for patients in the radiotherapy arm with a commercial radiotherapy treatment planning system (Varian Eclipse) to facilitate planning and assessment of radiation dose effects on functional tissue.
- Maintaining an up-to-date spreadsheet of clinical and imaging data for all patient visits.
- Assisting the investigators with data analysis and report writing for conference abstracts and peer-reviewed journal articles.

Expected Outcome

Lung cancer is the most common cancer in Yorkshire, with over 4,500 new cases diagnosed annually. Survival rates in the UK lag behind those seen in Europe and are greatly influenced by numbers able to undergo curative treatment with surgery or radiotherapy. Survival in Yorkshire is sadly currently below the UK average as high levels of respiratory co-morbidities reduce lung function and significantly increase the risk of serious adverse effects from either treatment. This study investigates whether more accurate, reproducible and regionally quantifiable MRI measures of lung function and structure, developed and translated in Sheffield, can be incorporated into current NHS diagnostic pathways and if the additional information gained alters treatment choice. These techniques will be focused on patients with borderline function where better selection for radiotherapy/surgery, potentially increases the number offered curative rather than palliative treatment and reduces the treatment risks, thereby improving survival and quality of life. It is also expected that the work will lead to conference proceedings at major national and international conferences and publications in reputable oncology and radiology journals.

Type of Project

Clinical project - based in the clinical environment with patients/including service evaluation

Additional Training

The student will be trained in medical image acquisition and analysis, specifically in the context of functional lung imaging. They will also be trained in the use of advanced software and programming and use of statistical software.

Role of nbas in human disease beyond bone fragility

Main Supervisor

Dr Meena Balasubramanian (m.balasubramanian@sheffield.ac.uk)

Second Supervisor

Professor Steve Renshaw

Aim and Objectives

- Analyse in-depth the skeletal, liver and immune abnormalities of homozygous mutant nbas fish.
- Recapitulate human phenotype, by generating disease-specific mutant zebrafish using CRISPR-Cas9.
- Drug screening assay to identify potential therapeutics.

The overarching hypothesis would be 'NBAS causes a multi-system disorder affecting skeletal development, liver and immune abnormalities in zebrafish: unravelling disease mechanism'.

Research Methodology

Whole genome sequencing studies have led to a vast amount of new candidate genes for human diseases. One such gene is NBAS (Neuroblastoma Amplified Sequence Gene) which when mutated results in acute liver failure and skeletal abnormalities (SOPH syndrome, Short stature; Optic atrophy; Pelger-Huet anomaly) [Maksimova et al., 2010]. Patients with NBAS mutations are subjected to a lifetime of recurrent fractures, repeated episodes of acute liver failure needing recurrent hospital admissions and immune deficiency [Balasubramanian et al., 2017]. Recently we have developed a zebrafish model which carries mutations in NBAS and displays skeletal malformations that are reminiscent of the human condition. Analysis done in my lab as well as others suggests that NBAS may play a role in the secretion of collagen.

Expected Outcome

Analyse skeletal and liver abnormalities in nbas mutant zebrafish
Compare with manifestations in Crispr fish
Drug screening to identify potential therapeutic hits for further work-up

Type of Project

Lab/Bench Project - primarily working in a lab environment

Additional Training

Genotype-phenotype correlation
Zebrafish genotyping
Skeletal analysis in zebrafish
Immune response in zebrafish model
Literature review of nbas phenotypes

This BSc project builds upon our work focusing on the zebrafish model to unravel the molecular causes of this disease and to develop a platform for high-throughput drug screens to identify drugs that may one day be used in the clinic. During your training year, you will use cutting-edge techniques such as lightsheet and AIRY scan microscopy, CRISPR/Cas9 gene editing and robot based drug library screening.

Exploring experiences of grief and current bereavement support services for ethnic minority communities

Main Supervisor

Dr Catriona Mayland (c.r.mayland@sheffield.ac.uk)

Second Supervisor

Dr Sarah Mitchell (s.j.mitchell@sheffield.ac.uk)

Third Supervisor

Nicola Turner

Aim and Objectives

The aim of the study is to explore views about the experiences of grief and the current provision of bereavement support within a specific ethnic minority community (South East Asian).
The objectives of the project are:
1. To establish the current knowledge about the experience of grief within a specific ethnic minority community.
2. To improve understanding about existing bereavement support provision, what works well and what is challenging in terms of meeting needs.
3. To explore experiences and improve understanding about what individuals / communities may want in terms of the type of bereavement support (informal and formal).
4. To develop guidance to inform local provision of bereavement support services.

Research Methodology

The project will focus on exploring the experiences of grief within a specific ethnic minority community and perceptions about the current levels of bereavement support provided. This will include key stakeholder engagement and qualitative interviews. It will help improve understanding about what individuals and specific communities may find beneficial in terms of bereavement support. The different components of the project are outlined as followed:
• A literature review focused on the experiences and language relating to grief and bereavement support within a specific ethnic minority community.
• Interviews with key stakeholders of bereavement support services about level of reach, barriers and facilitators to access.
• Interviews with individuals previously affected by bereavement.
• Thematic analysis of the interview data.
These components may be revised depending on individual needs and any potential ethical or practical issues.
The project builds on previous work from a systematic review, which synthesized existing evidence on bereavement care within the United Kingdom for ethnic minority communities (barriers and facilitators to access; models of care; outcomes from, and satisfaction with, service provision). The review revealed a stark lack of evidence about bereavement care for ethnic minority populations. In particular, understanding more about the role of family, friends and existing support systems, as well as engagement to help determine the most appropriate models and format of bereavement care were recommended.
 

Expected Outcome

Project outcomes will include:
1. The BSc thesis.
2. A summary of key recommendations to guide bereavement support.
3. Abstract to submit to relevant conference based on findings.
4. Manuscript for submission in peer review journal.
5. Presentation at Sheffield Palliative Care Research Network.

Type of Project

Qualitative Project/non-lab based - primarily using qualitative methods

Additional Training

The supervisor(s) are experienced in palliative care research (including engagement with bereaved relatives). Training will be provided to conduct literature reviews (also supported by trained librarians), research ethics, and qualitative data analysis. Interviewing practice will be provided by the supervisor. Opportunities to develop presentation and writing skills will be sought and well as opportunities to engage with relevant palliative care meetings e.g. Sheffield Palliative Care Research Network, Departmental Seminars in Oncology and Metabolism.

Use of Real World Data from the I-CAH registry to perform Analysis of Blood Pressure in patients with Congenital Adrenal Hyperplasia

Main Supervisor

Dr Nils Krone (n.krone@sheffield.ac.uk)

Second Supervisor

Dr Neil Lawrence (n.r.lawrence@sheffield.ac.uk)

Third Supervisor

Dr. Irina Bacila

Aim and Objectives

Congenital adrenal hyperplasia (CAH) is one of the commonest inherited disorders. CAH is associated with significant co-morbidity, in particular metabolic disease and cardiovascular disease. The impact of CAH on blood pressure in children and adults remains unclear from the literature, partly caused by the fact that only small patient cohorts have been studied. To solve this problem we will use real world data from the international congenital adrenal hyperplasia registry to establish the variation in blood pressure of patients throughout the world with CAH. Is systolic or diastolic blood pressure in patients with CAH higher, similar or
lower than healthy people of the same age and sex as defined by age and sex specific normative values? In patients under 18, does pubertal status have an effect on blood pressure in children with CAH?

Research Methodology

The student will be able to acquire a broad range of transferable skills and methods whilst conducting this research. We will compare biometric measurements with established normative data sets to establish standard deviation scores, and use mid parental height to calculate target height dependent upon patient sex. We will use R (a language and environment for statistical computing) to analyse data. Descriptive statistics will be used to broadly describe the data, with more sophisticated repeated measure within and between patient assessment being carried out with multiple change point analysis and multilevel modelling.

Expected Outcome

We will clarify the situation around blood pressure through access to this large data set. This will be incredibly useful for clinical practice and also lead to major scientific publications and dissemination at international conferences. A sophisticated statistical model that describes repeated measures of biometrics and blood pressure in patients with Congenital Adrenal Hyperplasia and allows quantification of the variability of blood pressure within patients with CAH as they age taking into account appropriate covariates will be produced, and allow sub analysis of patients on different treatment strategies, to detect whether different treatment strategies impact upon blood pressure.

Type of Project

Clinical project - based in the clinical environment with patients/including service evaluation

Additional Training

Statistical training from the University of Sheffield will be complemented by training in specific modelling packages. Students will be guided through free online courses to explore appropriate statistical packages to manage a large data set that has the challenges of missing data and data collected at varying time points. Basic knowledge of coding would be useful but is not mandatory. Work will be carried out in R, a language and environment for statistical computing, a free software platform. Methods taught in SPSS will be useful but exploring different software environments allows more versatility and power.

Decoding Pain: Applying Artificial Intelligence to Pain Neuroimaging

Main Supervisor

Dr Dinesh Selvarajah (d.selvarajah@sheffield.ac.uk)

Second Supervisor

Dr Kevin Teh (k.teh@sheffield.ac.uk)

Aim and Objectives

Pain is our body's alarm system, warning us either of danger in the environment, injury or the presence of disease. A unique and puzzling observation about pain is its distributed processing amongst multiple brain areas, informally called the pain matrix. Recently sophisticated new analytical methods that can decode complex patterns in data offer potentially more promising ways to interrogate pain related brain activity. Our aim is to identify a brain signature that characterises pain that can be used a biomarker for treatment response for clinical pain. If successful this will progress the development of personalised medicine and herald a major advance in the management of chronic pain.

Research Methodology

This is a clinical study involving patients with painful diabetic neuropathy. Each participants will attend two study visits. At the first visit we will performed clinical and neurophysiological assessments to characterise the severity of nerve damage and pain. On the second visit patients will attend for a magnetic resonance (MR) imaging brain scan to examine the brain regions involved in pain processing. You will be part of our research unit, working closely with our research fellow and MR data analyst to help with patient recruitment, perform clinical assessments and MR data analysis. We will teach you specific skills to perform neurophysiological assessments and how use machine learning algorithms to analyse brain imaging datasets.

Expected Outcome

Expected outcomes: 1. complete course objectives; 2. submit and present abstracts at conferences; 3. preparation and submission of manuscripts for publication.

Type of Project

Masters course

Additional Training

You will be taught how to perform detailed neurophysiological assessments e.g. quantitative sensory assessments, bedside nerve conduction studies using point of care devices and autonomic function assessments. You will also be taught to use machine learning algorithms to analyse MR imaging datasets.

Study of Pressure Sensing Insoles in Diabetic Foot Ulcer Recovery (STRIDER)

Main Supervisor

Dr Dinesh Selvarajah (d.selvarajah@sheffield.ac.uk)

Second Supervisor

Professor Solomon Tesfaye (solomon.tesfaye@nhs.net)

Aim and Objectives

One in four patients with diabetes will develop a foot ulcer and one in five patients with a foot ulcer requires an amputation. This is devastating for the patient and their family. It is also costly for the NHS. Over £119 million is spent each year in England on diabetes-related amputations. The numbers of amputations are rising and urgent action is needed to reverse this trend.

The lynchpin of foot ulcer care is pressure off-loading. The aim of this study is to examine if the use of smart-insoles, which provides real-time feedback of in-shoe foot pressure will accelerate the wound healing process in patients with diabetic foot ulcers.

Research Methodology

We are conducting a 12-week, open labelled study over 6 months. Twenty participants will attend six fortnightly visits to coincide with existing clinic appointments. All patients will receive the FEETME Smart Insoles system fitted in a DH walker. Smartphone application alerts (visual, tactile and audible) will notify users when foot pressure exceeds safe limits. Participants will be asked to walk a few steps or simply lift their foot up until the alert is turned off. At each study visit a photograph of the ulcer will be taken. The area will be measured using the ImageJ software. Ulcer healing is defined as complete wound skin closure which is maintained for 4 weeks.

Expected Outcome

You will be working with our research podiatrists on this study helping with recruiting study participants, performing study assessments at each visit, collating and analysing study data.

Type of Project

Masters course

Additional Training

The research training you will be provided during this BSc will be sufficient to complete this project.

Production and Characterisation of a Long Acting PTH fusion for treatment of Hypoparathyroidism (HypoPT)

Main Supervisor

Professor Richard Ross (r.j.ross@sheffield.ac.uk)

Second Supervisor

Dr Ian Wilkinson (i.wilkinson@sheffield.ac.uk)

Aim and Objectives

To test long acting PTH fusions for use in the treatment of hypoparathyroidism. To express, purify and test the bioactivity of these fusion molecules in a cAMP response assay. Evaluate the potential usefulness of these molecules to be taken in to in vivo work.

Research Methodology

The student will have ownership of the project throughout and will be trained in all necessary techniques in order to complete the project.

Phase 1: Growth & Expression of fusion molecules

  1. Grow & Express fusion molecules in a mammalian cell system.
  2. Purify fusion molecules using a combination of anion exchange and affinity chromatography.
  3. Assess purity using SDS-PAGE

Phase 2: Analysis and write up

  1. Test bioactivity of above constructs using a suitable in vitro bioassay measuring cAMP levels
  2. Conclusions & write-up

Expected Outcome

To fully analyse a PTH fusion in terms of purity and bioactivity for the potential further testing in vivo

Type of Project

Lab/Bench Project - primarily working in a lab environment

Additional Training

Training needs:

  • SDS-PAGE
  • Western blotting
  • PTH Bioassay (cAMP Assay)
  • Protein purification (Anion exchange & Affinity Chromatography)
  • Mammalian Cell culture technique
  • Teaching in use of various data analysis & handling packages: Lasergene, GraphPad prism (includes statistics package, ANOVA, t-tests), Excel
  • Effective report writing and presentation skills
  • Effective communication
  • Literature searching & Reading relating to but not inclusive:

Clinical need for a long acting PTH for treatment of hypoparathyroidism
Background to PTH: Mode of action
Competing commercial products

Clinical trial development for improved radiotherapy response

Main Supervisor

Dr Helen Bryant (h.bryant@sheffield.ac.uk)

Second Supervisor

Professor Sarah Danson (s.danson@sheffield.ac.uk)

Other Supervisors

Tim Mitchell

Aim and Objectives

Development of a phase one clinical trial protocol testing an Aurora Kinase Inhibitor combined with radiotherapy

Research Methodology

Clinical trial design methodology, Cell Tissue Culture, radiation assays Immunohistochemistry, Microscopy

Expected Outcome

The student will be part of the wider research lab group contributing to original research ideas. The student will be investigating the radio-sensitisation potential of two Aurora Kinase inhibitors. The student will also assist in the protocol design of a phase one clinical trial investigating the safety of combining an Aurora Kinase Inhibitor and Radiation. In addition there will be opportunities to assist with laboratory work investigating AURKA levels in cells and the mechanism of action of the combination therapy. The resulting work will contribute to at least one research paper and a poster/oral presentation at a meeting.

Type of Project

Lab/Bench Project - primarily working in a lab environment

Additional Training

Presentation skills, critical analysis, how to develop a clinical trial and lab specific skills will be taught by experienced staff within the supervisory team

The DNA damage response in Neuroblastoma

Main Supervisor

Dr Helen Bryant (h.bryant@sheffield.ac.uk)

Second Supervisor

Ruth Thompson

Other Supervisors

Dr Dan Yeomason, Dr David King

Aim and Objectives

Characterise the DNA damage response in Neuroblastoma cell lines
Test DNA damage response inhbitors in Neuroblastoma cell lines

Research Methodology

Tissue culture, RT-PCR, western blotting and immunohistochemistry

Expected Outcome

The student will contribute origional research to teh larger area of research in our lab. Specificalay they will identfy differences in the DDR between normal and Neuroblastoma cells. This will contribute to at least one research paper and a poster/oral presentation at a meeting

Type of Project

Lab/Bench Project - primarily working in a lab environment

Additional Training

The student will be trained in all the techniques above.

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