Intercalated BMedSci Degree

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 2022/2023

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.

External Partner Details: Not applicable 

Use of human tissue: Yes 

HBV vaccination required: Yes 

Ethics Approval: In place

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).

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)

External Partner Details: Not applicable 

Use of human tissue: Yes 

HBV vaccination required: Yes 

Ethics Approval: Not required

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.

External Partner Details: Not applicable 

Use of human tissue: Yes 

HBV vaccination required: Yes 

Ethics Approval: In place

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.

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.

∙ External Partner Details: Not applicable 

∙ Use of human tissue: Yes 

∙ HBV vaccination required: Yes 

∙ Ethics Approval: In place

For further information please contact Prof FM Boissonade on f.boissonade@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.

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).

External Partner Details: Not applicable 

Use of human tissue: No 

HBV vaccination required: No 

Ethics Approval: Not required

Availability, Properties and Attitudes to Oral Health and Cosmetic Products sold on  Internet

Supervisor: Prof P Hatton  

Background: 

There are a wide variety of substances and devices sold on the global market via the internet  that are claimed to improve oral health or cosmetic appearance. These include tooth  bleaching products, toothpastes, cosmetic orthodontic appliances, lip fillers, and temporary  filling materials. These invariably circumvent national laws and regulations related to quality  and safety, and appear to reach the UK market.

Aims: 

The aim of this project is to investigate the availability and risks associated with one or a  range of substances in these categories. 

Techniques/Methods: 

Using a range of research tools as relevant for the masters programme (including but not  limited to surveys, questionnaires, literature studies, chemical analysis, microbiology, and  cell culture to determine biocompatibility). The results of this research have the potential to  educate the public about hazards associated with internet "shopping" for oral products, and  inform government policy in this fast developing subject.

References: 

• Van Dyke S, Hays GP, Caglia AE, Caglia M. Severe Acute Local Reactions to a  Hyaluronic Acid-derived Dermal Filler. J Clin Aesthet Dermatol. 2010;3(5):32-35. Al Salehi et al., 2007  
• S.K. Al-Salehi, D.J. Wood, P.V. Hatton. The effect of 24 h non-stop hydrogen peroxide  concentration on bovine enamel and dentine mineral content and microhardness. J.  Dent., 35 (2007), pp. 845-850  
• Martin LHC, Hankinson PM, Khurram SA. Beauty is only mucosa deep: a retrospective  analysis of oral lumps and bumps caused by cosmetic fillers. Br Dent J. 2019  Aug;227(4):281-284. doi: 10.1038/s41415-019-0622-y. PMID: 31444444. 

External Partner Details: Not applicable 

Use of human tissue: No 

HBV vaccination required: No 

Ethics Approval: Not required 

For further information please contact Professor P Hatton on paul.hatton@sheffield.ac.uk

Validation of a Cerium-containing electrospun floreon antibacterial membrane as a  treatment for oral infection 

Supervisors: Dr J Shepherd (primary) Dr I Ortega (co-supervisor). Rawan Alshalan/Hollie Shaw (day to day supervisors)  

Background:

Chronic infections, wherever they are in the body, can greatly contribute to antimicrobial  resistance (AMR); this is mainly due to the persistence of bacteria deep within the infected  areas re-emerging, which causes recurrence of those infections requiring repeated cycles of  antibiotic treatment. To reduce the volume of antibiotics prescribed for such wounds, non antibiotic wound dressings have been developed such as those containing silver (e.g.,  Acticoat, Smith & Nephew). In previous work we have produced Floreon electrospun  scaffolds containing different formulations of cerium, a rare earth metal with antimicrobial  properties. We have pilot data testing the efficacy of this dressing on the common skin  wound pathogens Pseudomonas aeruginosa and Staphylococcus aureus.  

Aims: 

This project aims to develop and test a cerium-containing Floreon electrospun scaffold to be  used as an antimicrobial treatment to tackle chronic and recurring oral infections without  the use of antibiotics. 

Techniques/Methods:  

In this project we will expand this work set to include organisms relevant to oral infections  including anaerobes and Candida, and test any cytotoxicity of the scaffolds on human cells.  This is a lab based project that will involve microbiology and cell culture techniques. If  selected for a longer project this work may also involve electrospinning of the material.

References:  

• Farias, I.A.P., Santos, C.C.L.D. and Sampaio, F.C., 2018. Antimicrobial activity of cerium  oxide nanoparticles on opportunistic microorganisms: a systematic review. BioMed  research international, 2018.  
• Predoi, D., Iconaru, S.L., Predoi, M.V., Groza, A., Gaiaschi, S., Rokosz, K., Raaen, S.,  Negrila, C.C., Prodan, A.M., Costescu, A. and Badea, M.L., 2020. Development of  cerium-doped hydroxyapatite coatings with antimicrobial properties for biomedical  applications. Coatings, 10(6), p.516.  
• Kaygusuz, H., Torlak, E., Akın-Evingür, G., Özen, İ., Von Klitzing, R. and Erim, F.B., 2017.  Antimicrobial cerium ion-chitosan crosslinked alginate biopolymer films: A novel and  potential wound dressing. International journal of biological macromolecules, 105,  pp.1161-1165.  
• dos Santos, C.C.L., Farias, I.A.P., dos Reis Albuquerque, A.D.J., e Silva, P.M.D.F., da Costa  One, G.M. and Sampaio, F.C., 2014, October. Antimicrobial activity of nano 

External Partner Details: Not applicable 

Use of human tissue: No 

HBV vaccination required: No 

Ethics Approval: Not required 

For further information please contact Dr J Shepherd on j.shepherd@sheffield.ac.uk

PHH3 expression in Oral Dysplasia and its correlation with prognosis

Supervisors: Dr A Khurram, Dr H Mahmood and Dr N Azarmehr 

Background: 

Oral epithelial dysplasia (OED) is the precursor to oral squamous cell carcinoma (OSCC).  The incidence of OSCC is continually on the rise highlighting the need for new markers to  aid early detection. The current OED grading systems are subjective with significant inter and intra-observer agreement. One key feature that has been described in OED is the presence of increased numbers and abnormal forms of mitoses, which can be difficult to  analyse on H&E sections and are not quantified in diagnostic practice. Phosphohistone H3  (PHH3) is a mitosis-specific marker whose value has been validated in several tumours and  dysplasia. However, its role in OED remains largely unexplored.  

Aims: 

This project will explore the usefulness of PHH3 in identification and quantification of  mitoses as well as correlation with OED grade and progression.  

Techniques/Methods:  

This project will involve using approximately 100 cases including 30 from each grade of OED  (with 5-year follow-up and including cases transformed into OSCC) and 10 control cases  (including normal mucosa and OSCC). Immunohistochemistry for PHH3 will be performed  and the location and number of mitoses assessed using a light microscope and compared  with the H&E section. Quantitative evaluation will also be undertaken using QuPath and  correlation with risk factors, grade and OSCC progression carried out. You will get  experience in OED diagnosis, immunohistochemistry, digital pathology, imaging analysis and  relevant statistical methods. The findings from this project have the potential to aid OED  diagnosis and allow cancer risk prediction. 

References: 

• Malignant transformation in a cohort of patients with oral epithelial dysplasia.  Hankinson PM, Mohammed-Ali RI, Smith AT, Khurram SA. Br J Oral Maxillofac Surg.  2021 Mar 3:S0266-4356(21)00085-1. doi: 10.1016/j.bjoms.2021.02.019. Online ahead of  print. PMID: 34303542  
• Use of artificial intelligence in diagnosis of head and neck precancerous and  cancerous lesions: A systematic review. Mahmood H, Shaban M, Indave BI, Santos Silva AR, Rajpoot N, Khurram SA. Oral Oncol. 2020 Nov;110:104885. doi:  10.1016/j.oraloncology.2020.104885. Epub 2020 Jul 13. PMID: 32674040  
• A Novel Digital Score for Abundance of Tumour Infiltrating Lymphocytes Predicts  Disease Free Survival in Oral Squamous Cell Carcinoma. Shaban M, Khurram SA, Fraz  MM, Alsubaie N, Masood I, Mushtaq S, Hassan M, Loya A, Rajpoot NM. Sci Rep. 2019  Sep 16;9(1):13341. doi: 10.1038/s41598-019-49710-z. PMID: 31527658  
• Methods for Segmentation and Classification of Digital Microscopy Tissue Images. Vu  QD, Graham S, Kurc T, To MNN, Shaban M, Qaiser T, Koohbanani NA, Khurram SA,  Kalpathy-Cramer J, Zhao T, Gupta R, Kwak JT, Rajpoot N, Saltz J, Farahani K. Front Bioeng Biotechnol. 2019 Apr 2;7:53. doi: 10.3389/fbioe.2019.00053. eCollection 2019.  PMID: 31001524  
• QuPath: Open source software for digital pathology image analysis. Bankhead P,  Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, Dunne PD, McQuaid S, Gray RT, Murray LJ, Coleman HG, James JA, Salto-Tellez M, Hamilton PW. Sci Rep. 2017 Dec  4;7(1):16878. doi: 10.1038/s41598-017-17204-5. PMID: 29203879 

External Partner Details: Not applicable 

Use of human tissue: Yes 

HBV vaccination required: No 

Ethics Approval: In place 

For further information please contact Dr A Khurram on s.a.khurram@sheffield.ac.uk

Artificial Intelligence for automated analysis of radiology images and prediction of  pathology

Supervisors: Dr A Khurram, Dr N Azarmehr and Dr H Mahmood

Background:

The head and neck region is unique due to the diverse range of pathologies that can be seen  in this anatomical location. Out of these, lesions involving the maxillofacial bones are  particularly challenging as a number of these require radiographs and other imaging  modalities to arrive at a ‘provisional diagnosis’. A definitive diagnosis can only made once  tissue is removed which means that there is a risk of delayed and incorrect  diagnosis/treatment as radiological features can be misleading making it challenging to  differentiate between inflammatory lesions, jaw cysts, tumours and other lesions (i.e. fibro osseus). In some instances, a definite diagnosis may not be possible even on the biopsy as  the histologcal features can be non-specific or overlapping (as in fibro-osseus lesions or uni cystic ameloblastomas masquerading as a cyst). Artificial Intelligence is being widely applied  in cancer research as a useful diagnostic tool aiming to improve cancer diagnosis and  prediction. Use of AI has shown to remove the subjective analysis and variability in diagnosis  by ensuring standardisation and a quantitative output which can play a key role in informing  treatment decisions. However, its use in dental and maxillofacial radiology remains limited. 

Aims: 

This project will explore whether AI can help differentiate between a range of jaw lesions on  radiology alone..  

Techniques/Methods:  

This project will employ 500-1000 panoramic radiographs including common pathologies  such as ameloblastoma, odontogenic keratocyst, dentigerous cyst, radicular cyst, periapical  granulomas as well as fibro-osseus lesions (ossifying fibroma, cemento-osseus dysplasia and  fibrous dysplasia) as well as control cases (including normal jaw radiographs). The ground  truth/definitive diagnosis will be obtained from the pathology database and a bespoke  annotation tool will be used to outline the lesions and train the AI algorithms. After training,  the algorithms will be tested on unseen cases to determine whether they can differentiate  between the different pathologies based on radiology alone. Statistical correlation with site  and size of lesion as well as patient age and gender will also be carried out. The student will  work with a multidisciplinary team (NEOPATH- neopath.org.uk) receive training radiological  diagnosis and interpretation, related pathology, imaging analysis and relevant statistical  methods. The findings from this project have the potential to transform the future of  diagnosis for these lesions by making it more efficient, accurate and objective. 

References: 

• Artificial Intelligence-based methods in head and neck cancer diagnosis: an overview.  Mahmood H, Shaban M, Rajpoot N, Khurram SA. Br J Cancer. 2021 Jun;124(12):1934- 1940. doi: 10.1038/s41416-021-01386-x. Epub 2021 Apr 19. PMID: 33875821  
• Automated feature detection in dental periapical radiographs by using deep learning.  Khan HA, Haider MA, Ansari HA, Ishaq H, Kiyani A, Sohail K, Muhammad M, Khurram  SA. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021 Jun;131(6):711-720. doi:  10.1016/j.oooo.2020.08.024. Epub 2020 Aug 27. PMID: 32950425

External Partner Details: Not applicable 

Use of human tissue: No 

HBV vaccination required: No 

Ethics Approval: In place 

For further information please contact Dr A Khurram on s.a.khurram@sheffield.ac.uk

Investigation of effects of prolonged exposure to Chlorhexidine (CHX) mouthwashes  on CHX and wider Antibiotic resistance of oral bacteria

Supervisor: Prof G Stafford

Background:  

Antibiotic resistance is one of the largest threats to human health in the 21st century. In the  last 20 years a number of ‘over-the-counter’ broad spectrum antimicrobials have been  employed by dentists and used extensively by the public- with Chlorhexidine (CHX) the  most common. CHX is the active ingredient in a range of consumer oral mouthwashes (e.g  Corsodyl). Recent years has seen identification of isolates of hospital pathogens that are  resistant to CHX, via the action of multiple genetic elements. As part of routine oral health  and dental procedures, CHX, is commonly used at approx. 0.06-0.1%. Studies have shown  that prolonged exposure can transiently raise the inhibitory concentration of CHX to a range  of oral bacteria, with some evidence of effects on antibiotic resistance profiles- i.e. to the  commonly prescribed Metronidazole (MZ), Amoxicillin (AMX) or co-amoxiclav (CO-AMOX).  

Aims:  

In this project you will examine the emergence of CHX resistance and cross-adaptation to  MZ, AMX and CO-AMOX for a range of clinically isolated bacteria from various conditions in  the Sheffield collection; e.g. Porphyromonas, Tannerella, Enterococcus, Actinomyces and  Streptococci.  

Techniques/Methods: 

You will subculture bacteria at sub-inhibitory concentrations and test AMR after serial  passage and determine if strains with increased CHX resistance occur- and time permitting  begin their characterisation. 

References: 

• Verspecht T et al., Sci Rep. 2019;9(1):8326  
• Cieplik F, Jakubovics NS, Buchalla W, Maisch T, Hellwig E, Al-Ahmad A. Resistance  Toward Chlorhexidine in Oral Bacteria - Is There Cause for Concern?. Front  Microbiol. 2019;10:587. Published 2019 Mar 22. doi:10.3389/fmicb.2019.00587  
• Kitagawa H., Izutani N., Kitagawa R., Maezono H., Yamaguchi M., Imazato S. (2016).  Evolution of resistance to cationic biocides in Streptococcus mutans and  Enterococcus faecalis. J. Dent. 47 18–22. 10.1016/j.jdent.2016.02.008 

External Partner Details: Not applicable 

Use of human tissue: No 

HBV vaccination required: No 

Ethics Approval: Not required 

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

Sickly sweet - exploring the impact of glycans (sugars) on healthy ageing of the  mouth

Supervisor: Prof D Lambert

Background:  

A recent World Health Organisation report on healthy ageing begins: ‘The world is facing a  situation without precedent: We soon will have more older people than children and more  people at extreme old age than ever before.’ This illustrates starkly the importance of  research into healthy ageing, and underlies an explosion of interest in developing strategies  to reduce the burden of age-related disease; including those affecting the oral cavity, some  of the most common causes of a decline in quality of life in older people [1]. One of the key  features of ageing at the molecular level is the accumulation of ‘senescent’ cells in many  tissues, including those of the mouth [2]. Senescent cells lose the ability to divide but remain  alive, in many cases developing an inflammatory phenotype with detrimental effects on the  tissue in which they divide. Developing novel drugs to eliminate the effects of senescent  cells, and tools to monitor drug response, is an area of intense interest with considerable  clinical and commercial potential [2]. Many changes occur to cells as they become senescent,  including alterations in the expression of proteins and, as recently demonstrated by us and  others, the sugars (glycans) frequently bound to them [3]. Changes in the glycans decorating  proteins (the ‘glycome’) are found in a number of diseases, including those of ageing such as  periodontitis. These changes might have potential as a source of drug targets and/or  ‘biomarkers’ to help identify disease.  

Aim: 

The aim of this project is to build on work carried out with an industrial partner to  characterise the glycome of senescent oral cells.  

Techniques/Methods: 

You will use a range of molecular techniques to identify proteins and their associated sugars  on the surface of oral cells, and assess differences between young (dividing) and old  (senescent) cells. You will also interrogate datasets in collaboration with an industrial  partner and gain insight to the process of commercialising laboratory discoveries for patient  benefit. This project will provide experience of a number of laboratory techniques, data  analysis and visualisation, as well as providing opportunities to engage with an external  industry partner and gain experience of commercialising research in the context of oral  health. 

References: 

• Oral health for healthy ageing (2021) The Lancet DOI:https://doi.org/10.1016/S2666- 7568(21)00142-2  
• Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021)  DOI: https://doi.org/10.1038/s41580-020-00314-w 
• Qualitative and quantitative alterations in intracellular and membrane glycoproteins  maintain the balance between cellular senescence and human aging. (2018) DOI:  10.18632/aging.101540 

External Partner Details: Ludger Ltd 

Use of human tissue: No

HBV vaccination required: No 

Ethics Approval: Not required 

For further information please contact Prof D Lambert on d.w.lambert@sheffield.ac.uk

Lymphotactin in arthritis pain: Investigation of a novel biomarker for pain treatment

Supervisors: Prof F Boissonade (academic) and Dr Oscar Solis-Castro (day to day)

Background: 

Pain is a complex multidimensional experience that is poorly understood and sub-optimally  treated. Chronic pain affects an estimated 28 million people in the UK and in 75% of the  cases, pain is musculoskeletal, which includes pain caused by arthritis [1, 2]. Osteoarthritis  (OA) is the most common form of arthritis and the fastest growing cause of chronic pain  worldwide, affecting 9 million people in the UK [3]. Hence, there is a need to improve our  understating of the disease and the mechanisms involved in the development of OA pain in  order to develop better pain treatments. Among potential therapeutic targets, chemokines  have been found to mediate cellular and molecular pain mechanisms, which indicates that  modulating their activity could result in novel pain treatments [4]. Our laboratory has  established a relationship between the chemokine axis Lymphotactin (XCL1)-XCR1 and  neuropathic pain in rodents [5] and human tissue (unpublished). Our findings suggest a  novel role for the chemokine axis in pain processing and indicate its potential as a new  target for analgesics.  

Aims: 

The aim of the project is to investigate if the XCL1-XCR1 chemokine axis could have a role in  arthritic pain. Our hypothesis is that XCL1-and/or XCR1 are overexpressed in arthritic tissue  and the expression is associated to the level of pain.  

Techniques/Methods: 

To evaluate this hypothesis, rodent and/or human arthritic tissue will be processed and  analyzed to look at XCL1 and XCR1 expression (mRNA and/or Protein) and establish the  localization of these molecules within the synovium and joint tissue. The expression data will  then be correlated to clinical information obtained from the patients or mechanical pain  thresholds obtained from the rodent models. The techniques required for this project may  involve: Real-Time Polymerase Chain Reaction (RT-qPCR), ELISA, Immunohistochemistry  (IHC), Western Blot, fluorescent microscopy. 

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).  5. 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).

External Partner Details: Versus Arthritis (VA) 

Use of human tissue: Yes 

HBV vaccination required: Yes 

Ethics Approval: In place 

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

What our students say

Developing new skills

Alice Rigby Intercalated BMedSci Degree

Project title: Extracellular vesicles in HPV+ and HPV- oropharyngeal cancer and their effect on macrophages in the tumour microenvironment

Seeing a different side of the dental school

Aisling Power Intercalated BMedSci Degree

Project title: Targeting HOX/PBX Interactions in Head and Neck Cancer – Potential for Therapy?

Learning practical lab techniques

Heather Wallis Intercalated BMedSci Degree

Project title: Neural Stromal Interactions in the Tumour Microenvironment.

Getting a taste for academia

Chris Platis Intercalated BMedSci Degree

Project title: Targeting HOX-PBX Interactions in Head and Neck Cancer

Winning a junior Colgate prize

Paul Hankinson Intercalated BMedSci Degree

Project title: The role of Calmodulin Like 3 in the Development of Oral Cancer

Developing an understanding of oral microbiology, genetics and cell biology

Mary Connolly Intercalated BMedSci Degree

Project title: The role of outer membrane protein A in porphyromonas gingivalis biofilm formation and host cell interaction

Presenting at conferences and winning prizes

Hannah Crane Intercalated BMedSci Degree

Project title: The role of Interleukin-1 Receptor Antagonist in Head and Neck Squamous Cell Carcinoma

Gaining skills in appraising evidence

Christopher Chatham Intercalated BMedSci Degree

Project title: The role of lymphotactin in oral mucosal would healing

Presenting in Brazil

Dom Smith Intercalated BMedSci Degree

Project title: The role of RE-1-silencing transcription factor (REST)in head and neck squamous cell carcinoma (HNSCC) progression

Improving problem solving skills

Thomas Evans Intercalated BMedSci Degree

Project title: An examination of the adhesion and virulence of Candida albicans in vivo and in vitro

Gaining a variety of crucial biological lab skills

Joe White Intercalated BMedSci Degree

Project title: The Role of Tumour Suppressor HOPX in Oral Squamous Cell Carcinoma

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