Biominerals in Health and Disease
Lead Research Organisation:
University of Cambridge
Department Name: Veterinary Medicine
Abstract
Almost all biomedical research involves carbon-based (organic) molecules and yet we and other groups have shown that non-carbon based 'mineral' structures have unappreciated roles in supporting normal health and development. Moreover, we have found that by studying these mineral structures and function in biology we have new ideas on how to develop novel mineral-based therapeutics.. Much of our work concentrates on the digestive system and in understanding how our intestinal cells take up mineral structures and with what purpose. Our work integrates different disciplines, such as chemistry, cell biology, human nutrition and immunology, and we collaborate with many different scientists around the world. We then apply some of the lessons learned to other key medical research areas, such as the development of a mineral-based anti-cancer agent. Indeed we are very committed to translating our research findings for nutritional or therapeutic applications that will improve human health.
Specifically in this work we will describe:-
(a) How and why small mineral particles form naturally in the lumen of the intestine, and what their role is in acting as "cargo ships" that capture fragments of food and bacteria in this environment and then transport the cargo to cells of the intestinal immune system as a part of 'surveillance' for normal human health.
(b) Whether in Crohn's disease patients, the pathway described above is operating normally or not. And, if not, whether this may be secondary to the disease process or in fact carries a risk for the disease process to develop in the first place (i.e. cause or effect)?
(c) Whether engineered particles, to which we are all exposed via the diet or pills or personal care products, can hijack the pathway described above, lodge in intestinal cells and tip the balance between health and disease (notably Crohn's disease) in genetically susceptible individuals.
(d) Whether in fact the engineered particles to which we are exposed, as described in (c) get beyond the intestine and enter our blood circulation and therefore other tissues of the body. And if so, to what extent does this occur in healthy subjects and in those with Crohn's disease.
(e) Whether we can build mineral structures that will purposefully stimulate certain cell types for therapeutic benefit in diseases when the immune system needs a boost - such as in cancer.
Specifically in this work we will describe:-
(a) How and why small mineral particles form naturally in the lumen of the intestine, and what their role is in acting as "cargo ships" that capture fragments of food and bacteria in this environment and then transport the cargo to cells of the intestinal immune system as a part of 'surveillance' for normal human health.
(b) Whether in Crohn's disease patients, the pathway described above is operating normally or not. And, if not, whether this may be secondary to the disease process or in fact carries a risk for the disease process to develop in the first place (i.e. cause or effect)?
(c) Whether engineered particles, to which we are all exposed via the diet or pills or personal care products, can hijack the pathway described above, lodge in intestinal cells and tip the balance between health and disease (notably Crohn's disease) in genetically susceptible individuals.
(d) Whether in fact the engineered particles to which we are exposed, as described in (c) get beyond the intestine and enter our blood circulation and therefore other tissues of the body. And if so, to what extent does this occur in healthy subjects and in those with Crohn's disease.
(e) Whether we can build mineral structures that will purposefully stimulate certain cell types for therapeutic benefit in diseases when the immune system needs a boost - such as in cancer.
Technical Summary
Biomedical research is dominated almost exclusively by interests in organic molecules. However, we and others are showing increasing evidence for large inorganic structures (typically nanominerals) being involved in healthy cell communication and signalling and not just normal storage and structure or ectopic pathology, for which they are well known.
Our mission is to identify mineral structures and their cellular interactions in biology to further our understanding of human health and disease and, where appropriate, to exploit lessons learned through the engineering of novel mineral analogues that may offer fresh treatment modalities in human disease. We have a clear focus on nanoparticulate mineral structures, especially in terms of their occurrence and handling in the gastrointestinal tract. Over the next four years' of research we intend to (i) better describe why there are endogenous nanomineral pathways in the gastrointestinal tract and how these facilitate cell sampling of luminal macromolecules, (ii) demonstrate to what extent engineered nanoparticles, to which we are increasingly exposed, hijack these pathways and are systemically absorbed in humans, (iii) delineate whether dysfunction in the cellular handling of endogenous or exogenous nanomineral underlies the cause of Crohn's disease and (iv) show whether engineered nanoparticles can be exploited to establish selective cell activation and thus have immunotherapeutic properties (e.g. for cancer treatments).
Our mission is to identify mineral structures and their cellular interactions in biology to further our understanding of human health and disease and, where appropriate, to exploit lessons learned through the engineering of novel mineral analogues that may offer fresh treatment modalities in human disease. We have a clear focus on nanoparticulate mineral structures, especially in terms of their occurrence and handling in the gastrointestinal tract. Over the next four years' of research we intend to (i) better describe why there are endogenous nanomineral pathways in the gastrointestinal tract and how these facilitate cell sampling of luminal macromolecules, (ii) demonstrate to what extent engineered nanoparticles, to which we are increasingly exposed, hijack these pathways and are systemically absorbed in humans, (iii) delineate whether dysfunction in the cellular handling of endogenous or exogenous nanomineral underlies the cause of Crohn's disease and (iv) show whether engineered nanoparticles can be exploited to establish selective cell activation and thus have immunotherapeutic properties (e.g. for cancer treatments).
Planned Impact
Major potential beneficiaries of this work are as follows:-
a. Researchers studying gastrointestinal physiology and immunology, or nanotechnology, or particle science, or Crohn's disease or cancer.
b. Doctors looking for new angles in the cause and thus treatment of Crohn's disease or in the treatment of cancer.
c. Regulators and public health bodies aiming to better understand, and control, population exposure to persistent nanoparticles.
d. The population in terms of exposure to persistent oral nanoparticles.
e. Patients with Crohn's disease or cancer.
The above parties/stakeholders will benefit by the following mechanisms:-
a. Identity of new pathways for particle uptake in the gut.
b. Identity of new mechanisms for particles to carry bacterial and food fragments from the gut lumen to immune cells.
c. Knowledge of how these pathways/mechanisms described above could be exploited for therapeutic interventions.
d. Knowledge of what the systemic exposure to the population is for common persistent particles via the oral route and thus how this exposure can be better regulated.
e. Potential novel therapies for Crohn's disease or cancer.
a. Researchers studying gastrointestinal physiology and immunology, or nanotechnology, or particle science, or Crohn's disease or cancer.
b. Doctors looking for new angles in the cause and thus treatment of Crohn's disease or in the treatment of cancer.
c. Regulators and public health bodies aiming to better understand, and control, population exposure to persistent nanoparticles.
d. The population in terms of exposure to persistent oral nanoparticles.
e. Patients with Crohn's disease or cancer.
The above parties/stakeholders will benefit by the following mechanisms:-
a. Identity of new pathways for particle uptake in the gut.
b. Identity of new mechanisms for particles to carry bacterial and food fragments from the gut lumen to immune cells.
c. Knowledge of how these pathways/mechanisms described above could be exploited for therapeutic interventions.
d. Knowledge of what the systemic exposure to the population is for common persistent particles via the oral route and thus how this exposure can be better regulated.
e. Potential novel therapies for Crohn's disease or cancer.
Organisations
- University of Cambridge (Lead Research Organisation)
- Linkoping University (Collaboration)
- Health & Safety Laboratory (Collaboration)
- Charing Cross Hospital (Collaboration)
- University of Wales (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- SAS Trace Element Centre (Collaboration)
- Chalmers University of Technology (Collaboration)
- The Open University (Collaboration)
- UNIVERSITY OF LEEDS (Collaboration)
- SWANSEA UNIVERSITY (Collaboration)
- Laboratory of the Government Chemist (LGC) Ltd (Collaboration)
- National Institute of Scientific Research (INRS) (Collaboration)
People |
ORCID iD |
Jonathan Powell (Principal Investigator) |
Publications
Bastos C
(2020)
Robust rapid-setting antibacterial liquid bandages
Bastos C
(2020)
Copper nanoparticles have negligible direct antibacterial impact
Passos Bastos C
(2018)
Ligand-Doped Copper Oxo-hydroxide Nanoparticles are Effective Antimicrobials.
Description | CAPES PhD scholarship |
Amount | £163,881 (GBP) |
Organisation | Government of Brazil |
Department | Coordination of Higher Education Personnel Training (CAPES) |
Sector | Public |
Country | Brazil |
Start | 09/2017 |
End | 09/2021 |
Description | Research England GCRF QR Funding 2019-20 |
Amount | £80,000 (GBP) |
Funding ID | G102642 |
Organisation | University of Nairobi |
Sector | Academic/University |
Country | Kenya |
Start | 06/2019 |
End | 12/2020 |
Description | Analytical electron microscopy analysis (TEM, STEM, STEM-EDX) |
Organisation | University of Leeds |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided synthetic and biological specimens for analysis and expertise on these samples. |
Collaborator Contribution | Analytical electron microscopy analysis and advice. |
Impact | Peer-reviewed publications: PMID 27478107, 26863624, 25751305 |
Start Year | 2016 |
Description | Image based cell profiling |
Organisation | Swansea University |
Department | Centre for Nanohealth |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Data and expertise in human and rodent gastrointestinal anatomy |
Collaborator Contribution | Cell profiling technology |
Impact | Two publications: PMDs: 32445278, 32363770 |
Start Year | 2018 |
Description | Intracellular processing of calcium phosphate nanoparticles in human health and in Crohn's Disease |
Organisation | Open University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Financial contribution to a PhD studentship. Co-supervision of the PhD student. Access to research facility and expertise in calcium phosphate nanoparticles and Crohn's Disease. |
Collaborator Contribution | Experience and expertise in charactering intracellular calcium handling. Co-supervision of PhD student. |
Impact | None as yet. |
Start Year | 2017 |
Description | Investigations assessing intestinal antigen transport in health and disease |
Organisation | Linkoping University |
Department | Department of Clinical and Experimental Medicine |
Country | Sweden |
Sector | Academic/University |
PI Contribution | The research team will provide expertise for the processing, immunohistochemical staining and analyses of intestinal tissues and be responsible for the critical interpretation of the generated data. |
Collaborator Contribution | Linköping University is responsible for the sourcing, phenotyping, genotyping, coding and shipping of the study samples. Ussing chamber experiments will also draw on the experience and expertise of Linköping University. Linköping will be responsible for the critical interpretation of the generated data. |
Impact | No outputs as yet. |
Start Year | 2017 |
Description | NanoSIMS and TOF-SIMS analyses of bacteria and gut tissues |
Organisation | Chalmers University of Technology |
Department | Department of Biology and Biological Engineering |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Provided biological specimens and advice for these samples. |
Collaborator Contribution | Provide access to their research facilities and contributed their time for these analyses. |
Impact | No output yet, however peer-review publications are in preparation. |
Start Year | 2018 |
Description | NanoSIMS and TOF-SIMS analyses of bacteria and gut tissues |
Organisation | Chalmers University of Technology |
Department | Department of Chemistry and Chemical Engineering |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Provided biological specimens and advice for these samples. |
Collaborator Contribution | Provide access to their research facilities and contributed their time for these analyses. |
Impact | No output yet, however peer-review publications are in preparation. |
Start Year | 2018 |
Description | Quantitative Immunohistochemistry through In Situ Cytometry: Enhancing Bio-Analysis and Data Reproducibility |
Organisation | Swansea University |
Department | College of Engineering |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided tissue samples, access to research facility, methodology and advice on gut biology. |
Collaborator Contribution | Access to and continued development of In Situ Cytometry as a research tool for quantitative cell imaging. |
Impact | Publications pending. Submitted grants. |
Start Year | 2017 |
Description | Quantitative Immunohistochemistry through In Situ Cytometry: Enhancing Bio-Analysis and Data Reproducibility |
Organisation | University of Cambridge |
Department | Girton College |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided tissue samples, access to research facility, methodology and advice on gut biology. |
Collaborator Contribution | Access to and continued development of In Situ Cytometry as a research tool for quantitative cell imaging. |
Impact | Publications pending. Submitted grants. |
Start Year | 2017 |
Description | The analysis of titanium in whole blood - an inter-laboratory comparison to determine the best practise |
Organisation | Charing Cross Hospital |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | Provided the blood samples for the inter-laboratory comparison of titanium levels in whole blood. |
Collaborator Contribution | Provided results of their analysis of titanium in the whole blood samples. |
Impact | A peer-reviewed paper. |
Start Year | 2016 |
Description | The analysis of titanium in whole blood - an inter-laboratory comparison to determine the best practise |
Organisation | Health and Safety Laboratory |
Department | Biological Monitoring |
Country | United Kingdom |
Sector | Private |
PI Contribution | Provided the blood samples for the inter-laboratory comparison of titanium levels in whole blood. |
Collaborator Contribution | Provided results of their analysis of titanium in the whole blood samples. |
Impact | A peer-reviewed paper. |
Start Year | 2016 |
Description | The analysis of titanium in whole blood - an inter-laboratory comparison to determine the best practise |
Organisation | Laboratory of the Government Chemist (LGC) Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | Provided the blood samples for the inter-laboratory comparison of titanium levels in whole blood. |
Collaborator Contribution | Provided results of their analysis of titanium in the whole blood samples. |
Impact | A peer-reviewed paper. |
Start Year | 2016 |
Description | The analysis of titanium in whole blood - an inter-laboratory comparison to determine the best practise |
Organisation | National Institute of Scientific Research (INRS) |
Country | Canada |
Sector | Academic/University |
PI Contribution | Provided the blood samples for the inter-laboratory comparison of titanium levels in whole blood. |
Collaborator Contribution | Provided results of their analysis of titanium in the whole blood samples. |
Impact | A peer-reviewed paper. |
Start Year | 2016 |
Description | The analysis of titanium in whole blood - an inter-laboratory comparison to determine the best practise |
Organisation | SAS Trace Element Centre |
Country | United Kingdom |
Sector | Private |
PI Contribution | Provided the blood samples for the inter-laboratory comparison of titanium levels in whole blood. |
Collaborator Contribution | Provided results of their analysis of titanium in the whole blood samples. |
Impact | A peer-reviewed paper. |
Start Year | 2016 |
Description | The analysis of titanium in whole blood - an inter-laboratory comparison to determine the best practise |
Organisation | University of Wales |
Department | Centre for Advanced Welsh and Celtic Studies |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided the blood samples for the inter-laboratory comparison of titanium levels in whole blood. |
Collaborator Contribution | Provided results of their analysis of titanium in the whole blood samples. |
Impact | A peer-reviewed paper. |
Start Year | 2016 |
Company Name | NOBACZ HEALTHCARE LIMITED |
Description | Specialises in rapid set liquid dressing-bandages, including a product designed to help tackle digital dermatitis |
Year Established | 2019 |
Impact | A patented product, seed funding and 5 employees. |
Website | https://www.nobacz.com/ |