Biominerals in Health and Disease

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.

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).

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.