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Cell and Molecular Biology

Our dynamic and highly accomplished Cell and Molecular Biology research group studies molecular mechanisms important for cellular function in health and disease with a special emphasis on chronic diseases such as obesity, type II diabetes, cardiovascular disease, cancer and infertility.

Staff image of Prof Anne Graham

Our dynamic and highly accomplished Cell and Molecular Biology research group studies molecular mechanisms important for cellular function in health and disease with a special emphasis on chronic diseases such as obesity, type II diabetes, cardiovascular disease, cancer and infertility.

Cardiovascular disease

We investigate molecular mechanisms contributing to atherosclerosis (leading to heart attacks) and restenosis after heart bypass surgery in the ageing population and as a complication of diabetes.

We study inflammatory signaling pathways, angiogenesis, apoptosis and epigenetic modulators (e.g. non coding RNA), on functional responses of endothelial cells, vascular smooth muscle cells and platelets.

We are also developing multicellular models useful in tissue engineering.

A woman sitting with a cuff around her arm to measure blood pressure and heart rate

Blood pressure and heart rate monitoring

Diet and cancer

Cancer is a complex disease with many contributing factors.

Whilst it is clear that genetics plays a key role in determining predisposition to developing cancer, environmental factors also play a role and more importantly are modifiable risk factors.

For the cells lining the colon their environment is determined by the foods we eat. There is convincing evidence to show that foods containing dietary fibre decrease the risk of developing colon cancer, whilst red meat and alcoholic drinks increase this risk.

Research within the diet and cancer group is focused on understanding the molecular basis of these effects.

In particular, we are interested in how food products in the colon interact with the gut microbiota to bring about changes in the normal life cycle of the colon epithelial cells.

Staff image of Prof Anne Graham

Diet and Cancer

Cancer is a complex disease with many contributing factors. Whilst it is clear that genetics plays a key role in determining predisposition to developing cancer, environmental factors also play a role and more importantly are modifiable risk factors.

For the cells lining the colon their environment is determined by the foods we eat. There is convincing evidence to show that foods containing dietary fibre decrease the risk of developing colon cancer, whilst red meat and alcoholic drinks increase this risk.

Research within the diet and cancer group is focused on understanding the molecular basis of these effects. In particular, we are interested in how food products in the colon interact with the gut microbiota to bring about changes in the normal life cycle of the colon epithelial cells.

Genetics and Reproduction

There is considerable interest in genetic defects and disorders of male reproduction, and our work addresses such issues.

We can distinguish heritable genetic damage occurring preconceptionally from that induced during pregnancy and were the first to demonstrate that offspring could inherit damaged DNA from their smoking fathers. Thus, public health advice is now that hopeful Dads should not smoke for 3 months before conception.

There is a good correlation between DNA damage in sperm and lymphocytes, and we have devised a blood test to predict the chance of developing cancer based on DNA damage levels in these white blood cells.

We helped prove that sperm deliver not only DNA-encoded information to the egg at fertilisation but also epigenetic signals (heritable information not contained in the DNA). We are now investigating epigenetic damage in reproductive diseases.

Using bioinformatics, we discovered a protein expressed in the testes only when germ cells are dying and are studying its significance in infertility.

DNA damage in Blood Lymphocytes in the Comet Assay

DNA damage in blood lymphocytes in the comet assay

Neuroendocrinology

In the neuroendocrinology research theme we are investigating molecular mechanisms in body weight regulation.

The hypothalamus is the brain centre that is important in the regulation of body weight and food intake and whose dysfunction is associated with metabolic disorders such as type 2 diabetes and obesity.

We are interested in how the hypothalamus regulates long-term changes in energy balance and growth and integrates external environmental signals, such as the light/dark cycle or diet, to influence body weight and appetite.

Tanycytes, specialised glial cells in the hypothalamus are important in body weight regulation. The image shows tanycytes lining the third ventricle of the hypothalamus and was taken during an undergraduate student (H.Uddin, 3rd year project student 2017)

Specialised glial cells, tanycytes (in red), in the hypothalamus are important in body weight regulation

Currently available PhD opportunities in the area of Cell and Molecular Biology

Development of transdermal protein liposomal delivery system for the treatment of dermatological dis

Dr Mojgan Najafzadeh, Prof Diana Anderson, Dr Mohammad Isreb

A student in a Biomedical science lab.

Biopharmaceuticals have been increasingly used in the treatment of skin diseases. However, due to the poor absorption of peptide and protein through the skin, they are usually delivered through injections.

Encapsulation of protein in liposomes has been reported to provide a potential transdermal delivery system. Aspects such as sizing, lipid content and permeation enhancers could further improve the absorption of proteins through the skin.

The project involves the preparation of a nano liposomal drug delivery system using microfluidic reactors. The product will be tested in vitro using skin cell lines for efficacy and geno-toxicity. The project will be running in collaboration with the skin disease unit in St Lukes Hospital, Bradford, with a potential to expand the project into clinical trials.

Applicants are expected to be highly motivated and interested in research area involving aspects of drug delivery and cell cultures.

Entry requirements

2:1 honours in a relevant Bachelors degree or relevant Masters degree.

Funding

Applicants will need to have their own funding or external sponsorship. A bench fee may be payable in addition to the tuition fees.

Contact

Email
[email protected]; [email protected]; [email protected]
A student in a Biomedical science lab.

Dr Mojgan Najafzadeh, Prof Diana Anderson, Dr Mohammad Isreb

Electrophysiological changes in ion channels in human haploid and diploid cells

Dr Lijun Shang, Prof Diana Anderson, Dr Martin Brinkworth

Biomedical Science Lab

Nanomaterial-mediated delivery represents a promising technique for repro- and geno- toxicology with a potential to improve the safety and efficacy of existing methodologies, including experimental gene therapy and sperm-mediated gene transfer. However, their effects upon mammalian gametes with highly specialised structure and functionality remain under examined, especially their effects on the mechanisms of ion channel functions, although the University of Bradford is one of very few places where the spermatozoal nanotoxicology research has been undertaken for some time.

In this project, we plan to systematically investigate electrophysiological changes of the ion channels in human sperm cells, e.g. exposure to nanoparticles in the CatSper and Slo 3 channels in order to gain a deeper understanding of effects of these nanoparticles upon the function of the cells, for example, the main parameters of sperm function, including motility, viability, according to WHO guidelines and DNA fragmentation.

Our findings would provide useful information on the effect of nano versus bulk compounds on sperm and lymphocytes which might aid in therapeutic approaches. In addition, somatic lymphocyte cells after treatment with the same nanoparticles or bulk compound will be examined to determine differences in sensitivity between haploid and diploid cells.

Entry requirements

At least 2:1 Honours degree or equivalent in biomedical science, electrophysiology, toxicology

Funding

Applicants will need to have their own funding or external sponsorship. A bench fee may be payable in addition to the tuition fees.

Contact

Email
[email protected]; [email protected]; [email protected]
Biomedical Science Lab

Dr Lijun Shang, Prof Diana Anderson, Dr Martin Brinkworth

Impact of normal and premature ageing on human macro- and microvasculature

Dr Kirsten Suman-Riches, Dr Julie Thornton

Bioimaging equipment showing a microscope and screen with images

The global population is growing, with the number of births consistently higher than the number of deaths. This is because people are living for longer, due at least in part to improved lifestyle and healthcare provision. Consequently, in the UK 18% of the population are aged 65 or above. This equates to almost 12 million people thus factors relating to ageing health are of prime concern. In parallel with the increasing age of the population, we also have an increase in the number of individuals with Type 2 diabetes (T2D). This presents with features of premature ageing, and currently there are over 4 million patients in the UK alone with this disease, with a further 550,000 patients with T2D but without a formal diagnosis.

Problems with blood vessels are common to both ageing and T2D. These complications include the large blood vessels (macrovasculature), for example the development of atherosclerosis, and the smaller vessels (microvasculature) that can lead to issues such as poor wound healing. Another feature common to both ageing and T2D is systemic inflammation. This has led to an emerging research field into ‘inflammaging’ which can have a negative impact on blood vessels of all types. Studies on patients with T2D have revealed that keeping tight control of blood sugar levels can improve microvascular complications; however its impact on macrovascular disease is much more contentious. There is already evidence that macrovessels have differential gene expression dependent on their vascular source and disease state (Riches et al, 2014), hence it is very likely that there will be differences between micro and macrovessels when it comes to responding to the challenges of ageing and metabolic disturbances.

Blood vessels are composed of two main cell types. Endothelial cells (EC) line the blood vessel, and smooth muscle cells (SMC) are responsible for maintaining vessel tone and are the main cellular component of the vessel wall in macrovascular arteries and veins, and microvascular arterioles. In the very fine capillaries that underlie the skin, only EC are present. Ageing can lead to EC and SMC dysfunction, as can T2D. As yet, the mechanisms leading to cellular dysfunction in both scenarios have not been fully characterised.

Hypothesis

Gene expression differs between different vascular sources, even within the same individual. Identification of differentially expressed genes and the mechanisms leading to this will reveal new therapeutic targets to improve micro and macrovascular health in ageing and diabetes.

Aims

  1. Identify differences in the expression profile of whole vessels from different anatomical sites, with particular focus on inflammatory mediators
  2. Determine cellular source of altered transcripts, e.g. EC, SMC or both
  3. Determine the function and regulation of proteins from validated altered transcripts using cell culture models
  4. Evaluate any impact of age and/or T2D on these proteins by comparing expression and/or activity across multiple tissue donors

Experimental plan

The student will be trained in processing of human samples (saphenous vein representing the macrovascular and full thickness skin for isolating the microvascular arterioles). Samples from individuals of different ages and T2D status will be fixed, sectioned and used initially for immunohistochemistry (to familiarise the student with tissue architecture) and then for laser-capture microdissection to isolate specific areas of interest. Gene expression profiles of the matched micro- and macrovascular sites will be quantified using RNA sequencing or array. The cellular source of any transcriptional differential expression (e.g. SMC, EC) will be identified using fluorescence in situ hybridisation on sectioned tissue (years 1-2). The impact of differential expression will be evaluated using cell culture techniques. EC and SMC will be grown in isolation in culture from existing cell banks or from commercial sources, and over-expression and/or knockdown studies utilised to determine behavioural modulation (e.g. proliferation, migration), and the influence of ageing and T2D (years 2-3).

This project offers a number of opportunities for developing a programme of work that can be therapeutically applied to multiple clinical scenarios e.g. cardiovascular remodelling, wound healing.

Entry requirements

2:1 BSc (Hons) and/or merit at MSc level in Biology, Physiology or an allied subject.

Funding

Applicants will need to have their own funding or external sponsorship. A bench fee may be payable in addition to the tuition fees.

Contact

Email
[email protected]; [email protected]
Bioimaging equipment showing a microscope and screen with images

Dr Kirsten Suman-Riches, Dr Julie Thornton

Scaffolds for supporting epithelial cells

Prof. S. Rimmer, Dr W. Martin

Cells grown on hydrogel, A light microscope magnification of fibroblast cells growing on a hydrogel substrate - taken from a PhD student working for Professor Rimmer and used with his permission.

Tissue engineering requires the availability of polymer materials that can support cells and the development of tissues. Many synthetic materials are tough, easily fabricated and non-toxic. However, many synthetic materials can illicit immune responses to varying degrees. The best polymers in this respect are hydrogels containing little or no charge but high water content hydrogels are often weak materials and this limits their use. In this project we will bring together a number of aspects of our work in this area. We will use the observation that alkyl amines promote the growth of epithelial tissue, the synthesis of functional polymers using ozonolysis techniques, and the synthesis and cytocompatibility of conetworks.

Our aim will be to produce tough hydrogels based on polyurethanes (some of which will be degradable, with amine functionality for the support of epithelial cells and carboxylic acid groups for the support of other cells). The work will involve novel polymer synthesis, characterisation and cell culture, using techniques established in our laboratories.

Entry requirements

A 2i MChem or MSc in Chemistry or a related subject.

Funding

Applicants will need to have their own funding or external sponsorship. A bench fee may be payable in addition to the tuition fees.

Contact

Email
[email protected]; [email protected]
Phone
+44 (0) 1274 233362
Cells grown on hydrogel, A light microscope magnification of fibroblast cells growing on a hydrogel substrate - taken from a PhD student working for Professor Rimmer and used with his permission.

Prof. S. Rimmer, Dr W. Martin

Researchers within Cell and Molecular Biology

Prof. Anne Graham

Head of School of Chemistry & Biosciences, Professor of Biochemistry

Anne Graham

Study of human endothelial cell genetic and functional responses in health and inflammatory disease (atherosclerosis, diabetes, cancer). These cells lining the blood vessels play a key role in acute inflammation in health and chronic inflammation in disease. Low grade chronic inflammation at the blood vessel wall results in lesion formation and narrowing of the vessels (atherosclerotic plaques). Therefore cardiovascular disease and diabetes are key disorders where endothelial cells are dysfunctional.  Skin disease such as psoriasis also have a vascular component. Endothelial cells also have the ability to sprout and develop new blood vessels (angiogenesis), which is physiologically important but can stimulate metastasis in cancer. Intra-cellular signalling pathways important in endothelial cell proliferation, migration and apoptosis are currently under study in the Graham laboratory.

Orcid: 0000-0002-1810-3927

Twitter: @doctoranneg

Contact

Email
[email protected]
Phone
+44 (0) 1274 233570
Anne Graham

Head of School of Chemistry & Biosciences, Professor of Biochemistry

Prof Diane Anderson

Professor Diana Anderson

Professor of Biomedical Science and Established Chair

Dr Martin Brinkworth

Dr Martin Brinkworth

Associate Professor in Biomedical Sciences

Dr Gisela Helfer

Associate Professor in Medical Sciences

Dr Gisela Helfer

Dr Helfer studied Biology and Zoology at the University of Salzburg, Austria. During her Master’s studies at the University of Salzburg, she investigated the neurobiology of learning and imprinting behaviour of Japanese quail chicks. She then moved to the Max Planck Institute for Ornithology in Andechs, Germany, where she initially worked on the hippocampal formation of migratory birds with Prof Ebo Gwinner. At the Max Planck Institute, Gisela developed a strong interest in chronobiology (circadian rhythms and seasonality research) which lead her to take a research assistant post at the same Institute to work on the circadian system of birds with Dr Roland Brandstaetter and Dr Andrew Fidler.

In 2004, she commenced her PhD with Dr Brandstaetter at the University of Birmingham, where she graduated in 2007 for researching the molecular characterisation of the circadian system in passerine birds. After working as a teaching fellow at the University of Worcester, Gisela then took up a post as a research fellow at the Rowett Institute of Nutrition and Health, University of Aberdeen in 2009 working with Prof Peter Morgan. Her research at the Rowett focused on the seasonal neuroendocrine mechanisms regulating body weight and energy balance.

In 2016, Gisela moved to the University of Bradford, where she is a lecturer in Medical Sciences.

Contact

Email
[email protected]
Dr Gisela Helfer

Associate Professor in Medical Sciences

Dr Kirsten Riches Suman

Dr Kirsten Riches-Suman

Associate Professor in Biochemistry

Dr Jennifer Waby

Associate Professor in Biomedical Sciences

Dr Jennifer Waby

Jennifer Waby completed a PhD under the supervision of Dr Andrew Grierson and Professor Pamela Shaw at the University of Sheffield. Dr Waby's PhD was concerned with identifying the molecular mechanisms underlying axonal transport defects in motor neuron disease and focussed on the role of kinesin molecular motor proteins.

Upon completion of her PhD she went on to take up postdoctoral research associate posts with Dr Bernard Corfe, examining the impact of the fibre fermentation product butyrate on transcriptional regulation and later protein acetylation in colorectal cancer.

In 2010, Jennifer Waby secured an MRC VIP 3 month fellowship to allow her to pursue her own research interests.

This fellowship subsequently led to Dr Waby being appointed as a lecturer later the same year at the University of Hull. After spending five years at the University of Hull, Dr Waby moved to join Leeds Beckett University, teaching biochemistry to Nutrition and Dietetics students.

In January 2017 Dr Waby joined the team in the School of Chemistry and Biosciences, where she is presently teaching genetics, cell biology and pathology.

 

Orcid: 0000-0003-4729-6657
Twitter: @drwaby

Contact

Email
[email protected]
Phone
01274 235510
Dr Jennifer Waby

Associate Professor in Biomedical Sciences

Dr Munir Hussain

Dr Munir Hussain

Associate Professor in Biomedical Science

Dr Sobia Kauser

Dr Sobia Kauser

Assistant Professor in Biomedical Science

Dr Mojgan Najafzadeh

Dr Mojgan Najafzadeh

Assistant Professor in Medical Research