Intercalated BMedSci Degree

An intercalated degree involves an extra year of study, which is inserted between the years of the Bachelor of Dental Surgery (BDS) course, leading to the qualification of BMedSci.

Alice Rigby, dentistry student
On

Intercalation is an opportunity to obtain a deeper understanding of one of the subjects introduced in the BDS dental course, and will allow you to undertake a substantial research project. Research forms an essential part of your dental training, and this degree presents an early opportunity to develop research skills and potential.

An intercalated degree will also considerably enhance your CV, and broaden employment prospects. If you're interested in pursuing an academic career, it is even more worthwhile.

Although intercalating students do very diverse projects, all students have common aims and objectives that are fostered in the mandatory short course and in the supervisory element of the programme, as well as the your own self-directed study.

BMedSci (Intercalation) projects for 2021/2022

Development of an innervated 3D tissue-engineered oral mucosa model

Supervisors: Prof FM Boissonade, Prof DW Lambert, Prof C Murdoch and Dr HE Colley

Background:

Over the last decade our understanding of epithelial and stromal cell interaction has been greatly enhanced by the development of a wide range of 3D tissue-engineered constructs including models of skin and oral mucosa. These 3D tissue-engineered models can be used for a wide variety of purposes such as studies of toxicity, wound healing, tumour biology, and other skin disease. In addition to their uses for in vitro investigations, they are also beginning to deliver benefit in the clinic (usually in small-scale reconstructive surgery procedures). A number of cell types have been incorporated into these systems, thus allowing a closer approximation to the conditions found in human skin and oral mucosa in vivo. These cell types include keratinocytes, dermal fibroblasts and a range of immune cells. However to date there are very few models of skin or oral mucosa that incorporate neuronal cells.

There is now growing evidence that interaction between keratinocytes, fibroblasts and sensory neurones plays a significant role in both skin homeostasis and disease (eg wound healing, eczema and psoriasis). The neuropeptides calcitonin gene-related peptide (CGRP) and substance P have an established role in neurogenic inflammation and are thought to influence proliferation and morphogenesis of both keratinocytes and fibroblasts. Is it also well known that skin and oral mucosal cells produce a wide range of neurotrophic factors that have significant influence on neuronal development.

Aims:

To develop an innervated 3D tissue- engineered oral mucosa model, and study the effects of innervation on skin and mucosal morphology and response to injury.

Techniques:

A variety of cell culture techniques will be used. 3D oral mucosa and trigeminal ganglion neurones will be cultured using techniques developed in our laboratories. Successful co- culture will be determined by immunohistochemical identification of different cell types using methods that are well established in our laboratories.

References:

  • MacNeil S. Progress and opportunities for tissue-engineered skin. Nature 2007;445:874-880
  • Roggenkamp D, Kopnick S, Stab F et al. Epidermal nerve fibres modulate keratinocyte growth via neuropeptide signaling in an innervated skin model.
    J Investigative Dermatology 2013;133:1620-1628
  • Truzzi F, Marconi A, Pincelli C. Neurotrophins in healthy and diseased skin. Dermato-Endocrinology 2011;3:32-36
  • Yu XJ, Li CY, Xu YH, et al. Calcitonin gene-related peptide increases proliferation of human HaCaT keratinocytes by activation of MAP kinases.
    Cell Biol Int. 2009;33:1144-8
  • Colley HE, Eves PC, Pinnock A, Thornhill MH, Murdoch C. Tissue-engineered oral mucosa to study radiotherapy-induced oral mucositis. Int J Radiat Biol. 2013 Nov;89(11):907-14.

For further information please contact Professor F Boissonade on f.boissonade@sheffield.ac.uk

Viral smart missiles to combat antibiotic resistant infections

Supervisor: Prof G Stafford

Background:

While antibiotics have saved millions of lives since their introduction in the late 1940s, their efficacy is being increasingly curtailed by the rise in antibiotic resistance.  However, a solution in nature exists.  Since 1896 scientists have known of viruses that exist in the environment able to target and kill bacteria- these are known as bacteriophage.  These are species and often strain specific, and recent studies have begun to unlock their potential for use in human recalcitrant topical and systemic infections.

Dr Stafford’s team in Sheffield have developed techniques and isolated a range bacteriophage targeting pathogenic strains of Enterococcus (which contribute to oral endodontic infections as well as more serious septicaemias and diabetic foot ulcers).

Intercalation project image

Aims:

In this project you will attempt to isolate and study novel bacteriophage that kill the causative agents of Denture stomatitis and angular cheilitis- namely Staphylococcus aureus.  These will then be tested for their ability to clear biofilm infections.

A secondary aim will be to examine whether it is possible to isolate similar agents targeting the common oral infection Candida albicans- so called mycoviruses, using similar techniques.

Techniques/Methods:

  • Microbial culture and viral plaque assays
  • Transmission electron Micrography (to assess viral structure)
  • Genome sequencing (of isolated viruses)
  • Biofilm killing assays (using simple and complex models)

References

  • Identification of novel bacteriophages with therapeutic potential targeting Enterococcus faecalis. Al-Zubidi M, Widziolek M, Court EK, Gains AF, Smith RE, Ansbro K, Alrafaie A, Evans C, Murdoch C, Mesnage S, Douglas CWI, Rawlinson A, Stafford GP. Infect Immun. 2019 Aug 26. pii: IAI.00512-19.doi: 10.1128/IAI.00512-19
  • Fish R, Kutter E, Wheat G, Blasdel B, Kutateladze M, Kuhl S. (2018) Compassionate Use ofBacteriophage Therapy for Foot Ulcer Treatment as an Effective Step for Moving Toward Clinical.   Trials Methods Mol Biol. 2018;1693:159-170. doi: 10.1007/978-1-4939-7395-8_14.
  • Rebekah M. Dedrick, Carlos A. Guerrero-Bustamante, Rebecca A. Garlena, Daniel A. Russell, Katrina Ford, Kathryn Harris, Kimberly C. Gilmour, James Soothill, Deborah Jacobs-Sera, Robert T. Schooley, Graham F. Hatfull & Helen Spencer (2019)
  • Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus.   Nature Medicine volume 25, pages730–733 (2019)

For further information please contact Dr G Stafford on g.stafford@sheffield.ac.uk

An in vitro models of human salivary gland tumours

Supervisors: Dr L Bingle and Dr A Khurram

Background:

Salivary gland tumours are uncommon but histologically heterogeneous and so are often very difficult to diagnose, even for experienced pathologists. They most commonly occur in the major glands but are also relatively frequently found in the minor glands associated with the palate. Very little is known about the pathogenesis of tumour growth and development but associations with the presence of novel fusion proteins and viral infections has been established.

Hypothesis/Aim:

The aim of this project is to establish in vitro models of human salivary gland tumours, as an in vitro model, replicating the complex glandular structure, would provide an extremely useful tool to investigate tumourigenesis and could also have potential as a first screen for the novel biomarkers desperately needed as prognostic/diagnostic tools.

Method/Experimental plan/Techniques:

We have already developed 3D models of normal, human salivary glands from excess surgical tissue. We will similar methods to grow 3D tumour models using tissue from human salivary gland tumours as our starting material. We aim to develop a number of models with different cell phenotypes to reflect the heterogeneity of salivary gland tumours. These will allow us to determine the processes involved in the development of a tumour, particularly the role of fusion proteins and viruses. Functional assays will allow characterisation of the aggressiveness of tumours in relation to cell phenotype, heterogeneity and involvement of fusion proteins.

For further information please contact Dr L Bingle on l.bingle@sheffield.ac.uk

Neural–stromal interactions in tumour progression

Supervisors: Prof FM Boissonade and Prof DW Lambert

Background:

There is growing evidence that neural mediators play a role in the tumour microenvironment, and they have been implicated in tumour progression in breast, pancreatic and prostate cancer. However, the molecular mechanisms underlying their effects are poorly understood. Our recent studies have demonstrated significant cross-talk between neurones and oral squamous cell carcinomas (OSCC) cells.

We have identified receptors for specific neural mediators in OSCC-derived cell lines and have demonstrated that neural mediators have significant chemoattractant and proliferative effects on these cell lines. We have also shown that nerve growth factor (NGF) is elevated in OSCC-derived cell lines (relative to normal oral keratinocytes), and that NGF secretion from cancer-associated fibroblasts (CAFs) is significantly increased compared with that from normal oral fibroblasts. These findings suggest that neural mediators are capable of enhancing proliferation and migration of OSCC cells – potentially enhancing tumour progression – and that OSCC cells and CAFs may influence nerve growth in tumours (Fig. 1). Thus neuronal factors may have potential as therapeutic targets for cancer treatment.

Intercalation project image
Figure 1. Left – co-culture of trigeminal ganglion neurones and OSCC cells. Centre and right – cultures of trigeminal neurones in absence (centre) and presence (right) of media from OSCC cells.

Aim:

To further evaluate the effects of neural mediators and their antagonists on proliferation and migration of OSCC-derived cell lines alone and in the presence of other cell types, and to identify the mechanisms underlying these effects.

Techniques:

Quantitative polymerase chain reaction (qPCR) and immunocytochemistry will be used to identify specific neural mediators and components of their receptors in normal oral keratinocytes (NOKs); dysplastic, cancerous and metastatic cell lines; and neurones. Co-culture systems, cell proliferation and migration assays, will be used to identify functional cross-talk between neurones, cancer cells and fibroblasts (the predominant cell type of the tumour microenvironment). Enzyme-linked immunosorbent assays (ELISA) and qPCR will be employed to identify secreted factors involved in neural–tumour interactions.

This project will identify specific neural mediators and receptors that affect OSCC cell migration and proliferation, and that may provide novel targets for cancer treatment.

A short video related to this work can be seen at: https://youtu.be/QgZdtRd6FPI

References

  • Hoffmann P, Hoeck K, Deters S, et al. Substance P and calcitonin gene related peptide induce TGF-alpha expression in epithelial cells via mast cells and fibroblasts. Regul Pept 2010; 161: 33–37.
  • Magnon C, Hall SJ, Lin J, et al. Autonomic nerve development contributes to prostate cancer progression. Science 2013; 341: 1236361.
  • Toda M, Suzuki T, Hosono K, et al. Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide. Proc Natl Acad Sci USA 2008; 105: 13550–13555.
  • Venkatesh H, Monje M. Neuronal activity in ontogeny and oncology. Trends Cancer 2017; 3: 89–112.
  • Yu XJ, Li CY, Xu YH, et al. Calcitonin gene-related peptide increases proliferation of human HaCaT keratinocytes by activation of MAP kinases. Cell Biol Int 2009; 33: 1144–1148.
For further information please contact Prof FM Boissonade on f.boissonade@sheffield.ac.uk
In-situ immunohistochemical description of stem cell markers in the human dental pulp

Supervisors: Prof F M Boissonade, Dr O Solis Castro. 

Background: 

Stem cells sourced from the dental pulp have been studied widely for their potential in regenerative medicine, including research by our goup1. However, most studies rely on the characteristics of dental pulp stem cells in vitro, where they are identified by markers that may not represent the true phenotypic identity of these cells in their in vivo niche2. 

In vivo, there is support for a putative stem cell niche located in the perivascular region of the human dental pulp identified by the marker STRO-13. More recently the use of STRO-1 as a marker for a stem cell population in vivo has been supported by using direct isolation and characterization of cells from pulp tissue by cell sorting 4. 

Notably, the lack of evidence on the in vivo human dental pulp stem cell niche is due to the clear ethical and technical limitations of studying human patients. However, our lab has expertise in use of human dental pulp sections (collected from patients attending for extractions) to study a range of neuronal markers and compare their expression in relation to the degree of caries 5, and we have recently identified STRO-1 positive cells in this tissue (see figure below). Hence, we propose to follow this approach to compare the STRO-1 niche in samples with various degrees of caries. We hypothesize that the stem cell population expressing STRO-1 can modify their proliferation and position within the dental pulp as a response to the damage caused by caries.

Intercalation project image

Aims:

To identify and compare STRO-1 expression from dental pulp extracted from normal and carious teeth. 

Techniques/Method:

Histological techniques, immunohistochemistry, fluorescent microscopy, image analysis.  

References:

  • Solis-Castro, O. O., Boissonade M., F. & Rivolta N., M. Establishment and neural differentiation of neural crest-derived stem cells (NCSCs) from human dental pulp in serum-free conditions.  Stem cells translational medicine, doi:10.1002/sctm.20-0037 (2020).
  • Sharpe, P. T. Dental mesenchymal stem cells. Development 143, 2273–2280,doi:10.1242/dev.134189 (2016).
  • Shi, S. & Gronthos, S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. Journal of Bone and Mineral Research 18, 696-704 (2003).
  • Pisciotta, A. et al. Use of a 3D floating sphere culture system to maintain the neural crest-related properties of human dental pulp stem cells. Front. Physiol. 9, 547, doi:10.3389/fphys.2018.00547 (2018).
  • Rodd, H. D. & Boissonade, F. M. Innervation of Human Tooth Pulp in Relation to Caries and Dentition Type. Journal of Dental Research 80, 389-393, doi:10.1177/00220345010800011601 (2001).

For further information please contact Dr O Solis Castro on o.soliscastro@sheffield.ac.uk

Characterisation of nociceptors derived from human dental pulp stem cells

Supervisors: Prof Fiona Boissonade, Dr Oscar Solis Castro. 

Background:

Chronic pain affects more than one third of the UK and world populations. Healthcare costs of managing chronic pain exceed those of heart disease, cancer and diabetes; current treatments are ineffective in up to 40% of patients and often have severe adverse effects. It is the most common cause of years lived with disability in the world and in the UK alone 28 million people suffer from this condition.1 Thus it represents a major area of unmet clinical need.

The neurobiology of pain is poorly understood and this limits treatment options. However current evidence suggests that a more targeted approach could lead to more effective treatment. In particular, relevant research in human tissue is needed to further understand the pathogenesis of pain. Therefore novel, relevant tools for modelling human pain are urgently required.

We have recently shown that human dental pulp cells (hDPCs) can be induced to resemble cells known as neural crest stem cells (NCSC), which during development acts as a progenitor population that give rise to several specialized cells, including neurones. We have also shown that our hDPC-NCSCs are capable of differentiating into neurons (see image below) that can be further studied 2. 

However, to study pain a specific neuronal type called a nociceptor is required, these are primary sensory neurons that are critical in pain processing. Recent reports from other groups have shown that the transcription factor PRDM12 is a key factor in nociceptor development during embryogenesis and for pluripotent stem cell differentiation in vitro 3-5. Hence, inducing the expression of PRDM12 in hDPC-NCSCs should lead to specific differentiation into nociceptors that could be utilised to study pain in human cells. In addition to the use of these for in vitro modelling of pain, successful differentiation would bring a whole new scope for the use of these cells, as they can be collected from patients suffering from both congenital and acquired conditions associated with chronic pain.

Intercalation project image

Aims:

To obtain nociceptive neurons from neural crest-like stem cells derived from human dental pulp stem cells.

Techniques/Methods:

Cell culture of human dental pulp cells, PRDM12 transient transfection, neurosphere formation, neuronal differentiation, Immunocytochemistry and RT-QPCR.

References:

  • Fayaz, A., Croft, P., Langford, R. M., Donaldson, L. J. & Jones, G. T. Prevalence of chronic pain in the UK: a systematic review and meta-analysis of population studies. BMJ Open 6, doi:10.1136/bmjopen-2015-010364 (2016).
  • Solis-Castro, O. O., Boissonade M., F. & Rivolta N., M. Establishment and neural differentiation of neural crest-derived stem cells (NCSCs) from human dental pulp in serum-free conditions  Stem cells translational medicine, doi:10.1002/sctm.20-0037 (2020).
  • Chen, Y.-C. et al. Transcriptional regulator PRDM12 is essential for human pain perception. Nat Genet 47, 803-808, doi:10.1038/ng.3308 (2015).
  • Desiderio, S. et al. Loss of Prdm12 affects nociceptor differentiation in the mouse. Mechanisms of development 145, S116-S116, doi:10.1016/j.mod.2017.04.314 (2017).
  • Desiderio, S. et al. Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA. Cell Rep 26, 3522-3536.e3525, doi:10.1016/j.celrep.2019.02.097 (2019).

For further information please contact Dr O Solis Castro on o.soliscastro@sheffield.ac.uk

What our students say

Jamie Hall talks about his experience of the BMedSci programme at the University of Sheffield School of Clinical Dentistry.

Heather Wallis talks about her experience of the BMedSci programme at the University of Sheffield School of Clinical Dentistry

More information about the BMedSci (Intercalated degree)

Programme aims
  • To provide an enhanced knowledge and understanding of biomedical research and its methods
  • To develop skills in research evaluation, communication and ethics
  • To allow you to apply the above through an extended research project
Programme outcomes
  • The place of research in dentistry
  • Current dental research and its methods
  • The conduct of research in accordance with correct research methodologies and procedures
  • The importance of conducting research in accordance with up-to-date ethical guidelines and policies
  • The fundamental principles of designing research projects and protocols
Academic and intellectual skills
  • Design a research project in accordance with appropriate research methodologies and ethical principles
  • Exercise independent judgment and critical thinking
  • Apply basic statistical methods to data evaluation and interpretation
  • Present work orally and in writing to an academic audience
  • Where their project requires it, carry out practical experiments and tasks in a laboratory setting in accordance with health and safety guidelines
  • Produce a well-structured and substantial dissertation to present the results of their research project
  • Conduct an extensive literature review using relevant sources
Transferable skills
  • Apply good time-management skills to structure their work and meet deadlines
  • Effectively use a wide range of IT packages for a variety of tasks
  • Work independently on a project
  • Display good written and oral communication skills
  • Understand and apply basic statistical methods
  • Self-direct their learning
Taught element

If you undertake the BMedSci, you are required to attend a taught element of the programme. The taught element consists of the following designed to support the research experience:

  • Medical Research Skills
  • Ethics for Medicine
  • Applied Statistics for Medical and Health

Medical Research Skills

This module will run over the entire length of the course with activities occurring at least once a month.  The aim of the module is to provide training in key research skills, including critical appraisal of research publications, information literacy, hypothesis testing, experimental design, scientific writing, poster generation, and oral presentation skills. The module will be assessed by a critical appraisal of a publication related to the student’s research project.

Ethics for Medicine

The ethics module will run over the first 8 weeks of the BMedSci and includes lectures, tutorials, practical sessions and online training.  The module aims to help students to form their own opinions and provides them with the tools and knowledge that they may need to discuss and deal with ethical issues in medicine, including good clinical practice training. The  module will be assessed by a group ethics presentation and a short reflective essay.

Applied Statistics for Medical and Health researchers

The Statistics module will run over 9 weeks and will comprise of lectures, tutorials and practical sessions, including guidance on SPSS. The module will cover fundamental statistical concepts, and both simple statistical methods and the more widely used advanced methods of multiple linear regression and survival analysis.  It will be an applied module, equipping students with the knowledge and skills necessary to analyse a study to answer specific research questions; to understand and critically appraise the literature and to present research findings in a suitable fashion. The lectures will be delivered online with students expected to attend for tutorial sessions. The module will be assessed by analysis of a quantitative data set using SPSS, with students answering a number of research questions in a structured format

Summative assessment

The three elements comprising the summative assessment of the BMedSci are:

  • Medical Research Skills worth 10% of the final mark
  • Ethics for Medicine worth 10% of the final mark
  • Applied Statistics for Medical and Health worth 10% of the final mark
  • Dissertation worth 70% of the final mark
External employment

In accordance with the guidelines set out in the University’s Students’ Charter, students are reminded that they are advised to undertake no more than 16 hours of external work per week in addition to that required by their programme of study.

Research within the School of Clinical Dentistry

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Prizes awarded to BMedSci Graduates

Sheffield Prizes: British Society for Oral and Dental Research Junior Colgate Prize:

2011, 2012,2013, 2015, 2017, 2018, 2019

2011 Dominic Smith;
Tom Evans 2nd

2012 Hannah Crane

2013 Joe White

2015 Paul Hankinson

2016 Chris Platais

2017 Heather Wallis

2018 Zahra Kidy

2019 Alice Rigby

IADR Hatton Prize (international)
2018 Heather Wallis - runner up

INSPIRE 2016:
Jamie Hall Oral Presentation,
Heather Wallis Poster Prize

Royal Society of Medicine, Colyer Prize 2020
Zahra Kidy

Students have also been invited to present their work at other national and international meetings:

Applied and Integrated Medical Sciences intercalators conference, Bristol

BDA/Dentsply student scientist award, Wicklow, Ireland and London

IADR: Seattle, USA; Brazil

PER/ IADR Helsinki, Finland, Sept 2012

IADR Cape Town, South Africa, Summer 2014

INSPIRE Conference, London, October 2015

ABAOMS Conference, Sheffield, November 2015

INSPIRE Conference, Bristol, November 2018

IADR London, July 2018

IADR Vancouver, Canada, 2019

IADR Virtual meeting, 2020

Frequently asked questions 

What sort of work does the BMedSci involve?

This will really depend on the type of project you undertake. Everyone will do a statistics and ethics module, which is led by the medical school, and is assessed via coursework and a group presentation. The rest of your time is up to you to structure and will be very varied. Some projects will have lots of time spent in the different laboratories working with PhD students and also independently.

Will I be eligible for student finance during my BMedSci?

You will still be able to get student finance for a maintenance loan and to cover fees. However, the NHS bursary means even if you do the BMedSci you only need to cover 4 years of fees. This means that you’ll pay the fees during your BMedSci year but not during 4th or 5th BDS. There are also bursaries to apply for and whilst funding can’t be guaranteed there is often money available towards fees and /or living costs.

Will I deskill clinically during my BMedSci?

During your BMedSci you will still continue to have restorative dentistry clinics around once a week. Many previous students actually felt more confident clinically after their BMedSci and were also in the position of having done extra work to count towards their targets.

Will it be difficult fitting into a new year group?

During your BMedSci clinics you will join in with the year group below after the Easter holiday which is a good way to get to know people. You also end up with friends in both your original year and new year groups.

Is it OK if I’ve not had any research experience before?

Yes, most people will not have any research experience before starting their BMedSci. Supervisors are really helpful as are the PhD students in the different research groups. You also have the statistics and ethics teaching which can help too. The BMedSci is a great way to work out whether further research or an academic role would suit you in the future.

Why is it worth doing a BMedSci?

It is an interesting course which is very different to the BDS degree. It gives you chances to present your work at conferences and potentially become published. You also develop useful skills including independent working and an understanding of different scientific techniques.

If you have any further questions, you can complete our enquiry form.

Enquiry form 

For more information about the BMedSci (Intercalated degree), please contact:

Programme Lead
Professor Fiona Boissonade
f.boissonade@sheffield.ac.uk
0114 215 9314

Administrative Officer
Leyna Wright
leyna.wright@sheffield.ac.uk
0114 215 9304