Physiology and ecology of the neonatal gut microbiota

Duration of contract: 4 years 

Planned starting date: ASAP 
Place of work: University of Vienna/AIT
Main supervisor: David Berry

Project description:

Extremely premature infants, which are born before the 28th week of gestation and weighing <1,000 grams, are a highly vulnerable patient group. They frequently experience early-life brain injury that can lead to life-long neurological impairments. Recent research suggests that the gut microbiome can affect the immune system and brain development. As the neonatal gut microbiota-immune-brain axis is important in both short- and long-term neurological diseases, it is a promising target for early-life therapeutic intervention. In order to achieve this, a deeper understanding of the interplay between the microbiome, the immune system, and the brain in early life is urgently needed. This project aims to determine how dysfunction in the gut microbiota-immune-brain axis in extremely premature infants contributes to brain damage and long-term cognitive impairment. The molecular mechanisms underlying the etiology of these neurodevelopmental issues will be addressed in three project areas focused on the components of the axis: the gut microbiome, immune system, and brain.

The NeoGIBA project will take a stepwise, bottom-up approach to test how the gut communicates with the brain using cutting-edge model systems. Promising leads will be integrated in pre-clinical models to test novel intervention strategies. Specifically, we will determine interactions in the microbiome and how the microbiome communicates with the immune system. We will also dissect how cell-cell interactions propagate gut-derived signals to drive neuronal inflammation, focusing on immune cells as central mediators of the axis. We will characterize intestinal events preceding systemic inflammation and will test the impact of microbial components and inflammatory cues on microglial activation and neuronal cell development and physiology. We will then examine how a dysfunctional axis impacts cognition in pre-clinical models and an established patient cohort.

This project aims to make a major advance in the field by comprehensively investigating how the neonatal gut microbiome and its metabolites interact with the immune system and neurodevelopment. The project will provide fundamental insights into gut microbial ecology and immune- and neurodevelopment. It will contribute to novel translation-oriented strategies for early-life therapeutic interventions to improve the health of premature infants.

Position description:

We are looking for a highly motivated PhD candidate to develop, coordinate, and carry out the multidisciplinary project above. The candidate will be supervised by David Berry and will work in a team with other PhD students as well as Clarissa Campbell (host-microbe interactions and immunology, Centre for Molecular Medicine), Isabella Wagner (cognitive neuroscience, University of Vienna), Benedikt Warth (systems biology and metabolomics, University of Vienna), and Lukas Wisgrill (immunology and neonatology, Medical University of Vienna).

The candidate will be responsible for characterizing the microbiome and metabolome of extremely premature neonates using genome-resolved metagenomics and untargeted metabolomics. Additionally, they will characterize the physiology and ecology of isolates of the core gut microbiome. These results should provide insights into the function and assembly of the neonatal gut microbiota and serve as the basis for other work in the research team. Specifically, they will shed light onto the importance of species-specific physiological tolerances and capabilities as well as ecological interactions in determining microbiota assembly and succession. Additionally, they will inform practical strategies for promoting potentially beneficial microbes and conferring colonization resistance against important early-life enteric pathogens including Klebsiella pneumoniae and other pathobionts and immunomodulatory microbes.

The ideal candidate should meet the following criteria: background in microbiology, molecular biology, or related fields; experience working in a microbiology or molecular biology laboratory; programming skills (e.g., Python, R) and motivation to expand those; excellent written and spoken English; excellent skills in project planning and independency in problem-solving; ability to work in a multidisciplinary, international team. 

Experience with experimental design and gut microbiome analysis is strongly desired. 

(Optional) Skills list:

·        Anaerobic cultivation

·        Microbial physiology

·        Genomics analysis

·        Bioinformatics / mathematical modeling expertise

·        Experimental design

Apply now https://weblogin.univie.ac.at/idp/profile/SAML2/POST/SSO?execution=e1s2

How to apply https://vds-mes.univie.ac.at/application/current-call/how-to-apply/