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Biomedical Science PhD project opportunities

Find out more about self-funded PhD projects in areas of biomedical science.

We already have supervisors active and engaged in the research topic in our School of Life Sciences.

Research Group

Biomedical Research Group

Proposed supervisory team

Dr Grisha Pirianov

Prof David Leake (University of Reading)

Theme

Translational Biomedicine

Summary of the research project

Background: Macrophages play a critical role in homeostasis and diseases. They can change their phenotype to perform differential activities in different phases of inflammatory response.

Polarized macrophages are broadly classified into two groups:

  • classical activated M1 (pro-inflammatory)
  • alternative activated M2 (anti-inflammatory).

It has been demonstrated that M1/M2 switch plays critical role in inflammation which is dependent on various factors such as bioavailability of different subsets of monocytes and macrophages, sequential monocytes recruitment into the tissue in the process of inflammation or response to different conditions. Furthermore, the misbalance of M1/M2 switch can lead to chronic inflammatory diseases. Undoubtedly the generation of novel anti-inflammatory drugs regulating M1/M2 switch is an important step for pharmacological intervention of chronic inflammatory-based diseases. Unfortunately, the current drug screening strategies are not based on macrophage polarization. The development of a phenotypic macrophage high-throughput assay will provide a platform for screening of pro or anti-inflammatory properties of the candidate molecule (preclinical drug validation) or FDA approved drugs library and selected compound libraries with known anti-inflammatory activity (clinical drug validation).

Main goal and objectives: The main goal of the study is to develop and validate a novel phenotypic macrophage high-throughput cell-based assay for anti-inflammatory drug screening activity. The two main objectives are:

  • to develop a cell-based M0/M1/M2 phenotypic screen
  • to investigate the effect of novel small molecules (TLR4 antagonists) and selected compound libraries with known anti-inflammatory activity on M0/M1/M2 screen.

Methodology: Cell culture and cell-based essays, western blotting, ELISA approaches.

Collaborations: This project is based on academic and industrial collaborations with Reading University and Innaxon, UK respectively.

Outcomes: Results from this project will evaluate the potential of the phenotypic macrophage high-throughput assay for drug screening as well as provide important information about the effect of the candidate molecules on macrophage polarisation and will contribute to their preclinical/clinical validation. This will represent a finding of great public and commercial impact as currently there are no macrophage cell-based phenotypic assays for drug screening. The proposed project will have a commercial value and we plan to secure protection of the arising intellectual property.

Where you'll study

Cambridge

Funding

This project is self-funded.

Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.

Next steps

If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.

Research Group

Biomedical Research Group

Proposed supervisory team

Dr Grisha Pirianov

Dr Dannielle Green

Theme

Biomedicine and Environmental Pollution

Summary of the research project

Background: Plastic production has risen from 1.5 to 450 million tons annually since the 1950’s and is set to double by 2045. The total weight of plastic on Earth already exceeds the overall mass of all land and marine animals and plastic pollutants have altered Earth’s processes to an extent that exceeds the threshold under which humanity can survive in the future (i.e., surpassing the planetary boundary). Micro and nano plastics are the most abundant form of solid waste on Earth on average, humans are exposed to an estimated 39,000 to 121,000 particles per year via ingestion of contaminated food, beverages and drinking water via inhalation. The World Health Organization recently concluded that although NMP may pose a threat to human health, we need more evidence on their potential effects, especially concerning the lower size range (nano) of particles. In response to concerns about conventional plastics, demand for biodegradable bio-based plastics is increasing. Many of these plastics do not rapidly degrade in the natural environment and can persist as NMP and can have the same negative impacts as conventional plastics. The impacts of biodegradable NMP on human health has not been tested. Based on current knowledge on NMP toxicity and hazard there are substantial gaps and future research needs. Most of the studies are based on NMP without any characterisation of their physico-chemical properties (size, shape, charge etc.) which create difficulties in interpretation of their toxicological profile. Secondly, a high number of studies have employed very high concentrations of NMP which do not reflect on real environmental conditions. Although toxicological studies have shown that NMP exposure may lead to health risk there is a lack of evidence that this can negatively affect the immune system which is primary related to measurement of human health risks. Therefore, future research must be focused on biokinetics and proinflammatory and toxicological properties of environmentally relevant NMP with well characterised physico-chemical properties consistent with their environmental degradation.

Main goal: This project will investigate the proinflammatory and toxicological properties on NMP generated from conventional and future biodegradable plastics.

There are three main objectives:

  1. To develop THP-1 macrophage polarisation model as a biosensor for screening and comparison of proinflammatory and toxicological properties on NMP from different plastics.
  2. To screen the toxicological and proinflammatory effects of NMP from different plastics on the macrophage polarisation biosensor model.
  3. To investigate the mechanism of action of selected NMP candidates in relation to their toxicological and proinflammatory properties on the macrophage polarisation biosensor model.

Methodology: Cell culture and cell-based essays, western blotting, ELISA, Flow Cytometry and antibody array approaches.

Collaborations: This project is based on national and international academic collaborations with University of Milano-Bicocca and Reading University.

Outcomes: The results from this project will be used to consolidate international networking and national and international collaborations and to apply for EU Horizon (Micro- and nano-plastics in our environment: understanding exposures and impacts on human health) and will build on the success of the REF2027 Impact Case Study by Dr Green “Reducing the impacts of single use plastics”. This research also compared conventional and biodegradable plastics but on environmental compartments as opposed to human health.

Where you'll study

Cambridge

Funding

This project is self-funded.

Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.

Next steps

If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.