| Quantification of collagen turnover in musculoskeletal tissues in response to lifestyle interventions and disease |
The number of older people in the world is rapidly increasing, which also increases the number of conditions associated with ageing, including low bone mass (e.g., osteoporosis [OP]). OP is a major worldwide problem with >200 million women alone living with the disease. A significant clinical problem associated with OP relates to fragility fractures of the bone and, in England, >300,000 individuals suffer these each year, with >1100 deaths occurring in the UK each month due to hip fractures alone. Not only our bones, but also our muscles, ligaments and tendons, change as we get older and these changes can lead to other conditions, such as osteoarthritis (OA), which causes joint pain and stiffness. OA is also a major health issue for the ageing population, affecting ~8.5 million people in the UK. Bone mineral density (the amount of mineral [calcium] in bone) is considered a key predictor of OP fracture, although it only relates to about two-thirds of the bones strength. Other factors in the non-mineral compartments of bone are equally important. The extracellular matrix (molecules secreted by nearby cells to provide structure and support) of bone is largely made up of a protein called collagen, which is vital in providing underlying strength to the bone. Unfortunately, the normal and abnormal changes in bone collagen in health and disease are not well known because of a lack of good methods to measure it. We have developed an accurate method to determine musculoskeletal tissue collagen turnover in humans using “heavy water”; a form of water that has a heavier than normal hydrogen isotope (part of its chemical structure), meaning that we can measure where in the body it goes after it has been ingested. Our aim is to better understand the responses of collagen in the musculoskeletal tissues of healthy and diseased humans, leading us to examine potential intervention strategies to improve musculoskeletal health across the lifespan.
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| Enhanced nutritional value and tolerance to abiotic stress in crops through biostimulant (seaweed extract) and micro-nutrition |
The PhD project builds upon the success of a recent Innovate UK funding, in which we increased pepper nutritional value, shelf life, flavour, and heat/drought tolerance. For this project, we aim to develop a unique new formulation or programme of biostimulants and micronutrients that increases crop quality and abiotic stress tolerance. Plant biostimulants contain diverse substances and micro-organisms which are applied to plants or the rhizosphere is to stimulate natural processes to enhance/benefit nutrient uptake, nutrient efficiency, tolerance to abiotic stress, and crop quality. The worldwide market for biostimulants increases 12 % per year and will reach >$2,200 million in 2018. However, the mechanism of the biostimulant and micronutrients use efficacy is unclear. Understanding of the dynamic interactions between crop-physiological processes and metabolic processes, could help in identifying effective fertilizer nutrient composition and in developing next-generation fertilizers. The main aim of this project is to develop biostimulant formulations and micronutrient formulas that can enhance stress tolerance and improve plant growth and quality by using epigenetics. These will help clarify how specific biostimulants substances affect nutrient uptake, plant growth and stress-tolerance responses, and how these vary through different delivery systems (comparing foliar with root uptake)and timings. Also it will offer the potential to find markers for the crop breeding through product development of biostimulants. |
| Proteins and the human gut microbiota: who does what? |
The human gut microbiota represents a diverse community of bacteria, archaea, viruses and fungi; the collective gut microbiota genome (‘metagenome’) encodes 150 times more genes than the human genome. Enzymes encoded by the metagenome allow gut bacteria to use dietary substrates that escape digestion by human-encoded enzymes in the gastrointestinal tract. Metabolites produced from these microbial processes act on intestinal cells, or are taken up into the blood and transported around the body. The interaction of microbial metabolites and host cells – the so-called microbial–mammalian metabolic axis – contributes to homeostasis of the human system. Disruption of homeostasis and the gut microbiota is linked with a range of metabolic diseases (obesity, non-alcoholic fatty liver disease, atherosclerosis, type 2 diabetes), inflammatory bowel disease (Crohn’s, ulcerative colitis) and neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease). We only know the functions of ~30 % of the metagenome genes. While much is known about the bacteria responsible for fermenting carbohydrates in the gastrointestinal tract, little is known about the microbes that use proteins, peptides and amino acids in this environment. A diverse range of products are produced as a result of microbial-driven synthesis or proteolysis, which have the potential to influence host systems in beneficial or detrimental ways. This project is characterising proteolysis in a range of anaerobic gut bacteria. Understanding which gut bacteria are involved in proteolysis will allow us to develop targeted interventions to promote human health.
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