"The gut microbiota (100 trillion cells) outnumber human cells by 10 to 1. Its composition of around 500 to 1000 species is specific for each individual and is dynamic, changing with age, health and diet. It is now recognised that the collective human gut microbiota consists of some 35,000 species with most being located in the colon. The gut microbiota influence more than just host nutrition. For instance, the microbiota contributes to the development of the immune system, it protects us from invasive bacteria, it can affect the incidence of cardiovascular disease, and it also affects body weight, drug metabolism, IBD (e.g. Crohn’s disease and ulcerative colitis), colorectal malignancies, obesity and autism. Thus, the composition of the microbiota is a critical factor in human health.
One of the major nutrients affecting propagation of bacteria is iron. This transition metal is essential for nearly all organisms. Bacteria possess multiple iron-uptake systems in order to ensure a continued supply of this vital metal. Some bacteria can utilise haem as an iron source, many secrete ‘siderophores’ to solubilise ferric iron for eventual uptake. In addition, bacteria can acquire iron from host proteins (e.g. transferrin) and in the reduced (ferrous) form. Indeed, bacteria have the ability to reduce exogenous iron to render it soluble and available. Bacteria are also in competition for their iron resources and can pirate each-others ferri-siderophores. The microbiota is also in competition with the host for iron and may benefit from the host’s ascorbate-dependent ferric-reduction activity.
It remains unclear how iron regime influences the makeup of the intestinal microbiota and whether differences in iron regime that cause alterations if the gut microbiota have any consequential effects on the health- or disease-promoting activities of our microbiota. The aim of this research is to investigate this possibility. For this purpose, we will use gut models inoculated with human gut microbiota to determine how populations change as iron levels increase and decrease, and in response to difference iron sources (reduced, oxidised, complexed, haem, associated with proteins, or when chelated by molecules such as lactoferrin and tannins). We will measure the gut microbiota composition using NGS 16S rDNA community profiling. We will also measure health indicators such as short-chain fatty acid profiles. In addition, the impact of iron regime on the metatranscriptome of the gut microbiome will be determined, under steady-state growth conditions using a gut model. This will provide insight on the manner in which the microbiota, as an entire community, respond to changes in iron availability.
The project is collaborative with Prof Glenn Gibson in Food Microbiology and Dr Pereira (Pathology, University of Cambridge). The work could also involve human volunteers and appropriate animal models (e.g. piglets) to determine impact of iron regime on milk fed infants. We may be able to identify and study gut bacteria that have very strict metal/iron requirements, or metal/iron induced changes that influence health (e.g. obesity, early onset rheumatoid arthritis, colorectal cancer or IBD) since the components of the gut microflora that have profound effects on health and disease are now becoming clearer. Such studies may lead to findings that allow us to establish beneficiary dietary iron regimes.
Roles of specific bacteria iron acquisition systems in gut colonisation will also be explored. Since the human host employs an extracellular ferric-iron reduction system within the gut to obtain iron from the diet, the possible role of a similar bacterial system in mobilising iron for uptake by the human host will be tested.
The PhD programme will allow the applicant to experience a wide range of important molecular techniques (e.g. NGS, community profiling, metagenomics, metatranscriptomics, directed mutagenesis, cloning, gut models, metabolomics supervised by Dr Anisha Wijeyesekera) and will provide much scope for independence, publication and attendance at scientific conferences. The work is novel and exciting, and would be expected to lead to high impact outputs. The lab is well equipped and the candidate would join a well-established and supported group working on a set of related projects.
High quality International students with funding are strongly encouraged to apply. Many other related/unrelated projects are also available and details can be provided upon request. UK/EU students with an interest in this project should apply in good time so that funding sources can be identified and funding sought.
Eligibility requirements: Applicants should have a bachelors (at least 2.1 or equivalent) or masters degree in a biological subject (e.g. Biology, Biochemistry, Microbiology, Genetics, Biomedicine, Biological Chemistry, Molecular Biology, Food Sciences) or a strongly-related discipline.
"Andrews, S.C., Robinson, A.K. & Rodriguez-Quinones, F., (2003). Bacterial iron homeostasis, FEMS Microbiology Reviews, 27, 215-237.
Jenkins et al. Journal of Trace Elements in Medicine and Biology 49 (2018) 79–85 Obesity, diabetes and zinc: A workshop promoting knowledge and collaboration between the UK and Israel, November 28–30, 2016 – Israel"
Web link: http://ironmicrobiome.com/