PROJECT DESCRIPTION:
Epigenetic imprinting by microbial short-chain fatty acids and the influence on early onset of type 1 diabetes
There are 415 million people with Type I Diabetes Mellitus (T1D) and since 2000, the incidence of type 1 diabetes has been steadily increasing, especially in infants. Although T1D can be controlled by lifelong insulin therapy and self-monitoring, the development of approaches to prevent or delay onset is an important goal. Pregnancy is a critical period of plasticity whereby nutrition - one of the greatest environmental determinants - may influence foetal development but also exert a long-lasting impact on the offspring's growth, metabolic and immune health into adulthood. Several studies suggest that SCFAs are epigenetic modifiers that promote immunoregulation and ameliorate autoimmune diseases. Progression of diabetes is inversely correlated with blood concentrations of acetate. Here we propose to test whether feeding high amylose-resistant starches esterified with acetate or propionate to pregnant NOD mice can prevent onset of diabetes in their offspring through epigenetic imprinting in utero. We will investigate impact of these specialised maternal diets on selected cell types important in T1D from foetuses and offspring (3 weeks post-weaning). Results of assessing chromatin states, histone modifications and gene expression profiles will be integrated with functional properties to elucidate cellular mechanism leading to disease protection. The results of this study will greatly increase our knowledge on the epigenetic impact of microbial produced acetate and propionate on the foetus and offspring. Moreover, the use of resistant starches esterified with SCFA may be a useful approach to prevent or treat T1D and other diseases of modern societies.

WE ASK:

• Relevant Bachelor level education e.g. in the biology, molecular sciences and nutrition and health programmes.
• A Masters degree, with relevant practical experience (e.g. molecular microbiology, microbiota studies or immunology and cell biology).
• A professional, reliable and organised method of working.
• Good level of English (spoken and written).

WE OFFER:

• A challenging job for a period of 4 years (18 months with an extension of 30 months after successful evaluation) at an international leading organization. The organization has good and flexible employment conditions.
• A job in an international setting with varied work and plenty of opportunity for personal development in a pleasant and open working environment. The appointment is for 38 hours per week.
• In according to the Collective Labour Agreement (VSNU), the salary will increase from € 2.325,00 gross per month in the first year up to € 2.972,00 in the fourth year (38 hours).
• We offer 232 hours of leave for a full-time position of 38-hours per week, with the option of accruing another extra hours (compensation leave) for a 40-hour working week.
• 8% holiday allowance and a fixed 8,3% end-of-year bonus.
• The arrangements for special leave, parental leave and sick leave are above average, as is the employer's pension contribution.
• You can arrange the optimum balance between work and private life.
• We offer good training and education opportunities
• Sports facilities at reduced prices are at your availability

Wageningen University & Research

WE ARE
Research at the Host-Microbe Interactomics (HMI) Group ranges from work on the molecular mechanisms of diseases caused by pathogenic bacteria, to the interactions between pathogenic and beneficial bacteria and their human or animal hosts. The group, combines expertise in cell biology, immunology, microbiology and functional genomics to further our understanding of the molecular interactions occurring in the cross-talk between microbes and their hosts.
Research at the Nutrition, Metabolism and Genomics group is centred on expanding knowledge of the molecular physiology of nutrient metabolism in health and metabolic diseases and elucidating what key regulatory pathways go awry during disease development and aging. The three main research themes are: (1). Molecular regulation of lipid metabolism (2). Immunometabolism, adipose tissue, and metabolic health and (3). Nutritional regulation of intestinal health.

Wageningen University and Research delivers a substantial contribution to the quality of life. Within our domain, healthy food and living environment, we search for answers to issues affecting society and health. Every day, at WUR, 6,500 people work on 'the quality of life', turning ideas into reality.