Grant: Discovery Grants Program - Individual

The biological mechanisms regulating growth and development are not fully understood. This may be due to our limited understanding of how an organism's development is shaped through its interactions with the environment and other living things, including microorganisms, in early life. We do know that exposures early in an animal's development set its growth trajectory, prioritising growth for immediate survival. However, this strategy has known adverse consequences, including compromising immune function, which can influence fitness, behaviour and survival long-term. Despite this knowledge, there is limited data on how early life exposures impact organ systems that are critical for regulating both growth and cellular/biological defence mechanisms. Studying how these systems coordinate to support appropriate growth and immune function, and how their function is shaped by early environmental and microbial exposures, will uncover new fundamental knowledge about development and provide insight into physiological adaptations to early life challenges.The long-term objective of my research programme is to understand the genomic and biological mechanisms that regulate growth and development and how these mechanisms may be in conflict with those that support an animal's immune defences. To do this, an innovative approach is required that considers the cross-talk that occurs in early life between organ systems important for both growth and immune function. We will use a mouse model of maternal nutritional programming to induce poor growth. Using 16S gene sequencing and mass spectrometry we will determine how this nutritional environment affects the community of microbes inhabiting the birth canal that colonise the offspring during delivery, and the composition of the maternal milk, critical for offspring growth and establishing its immune defences. We will use RNA sequencing, histological techniques and brain imaging to uncover how malnutrition and poor growth alter functional genes and cellular pathways in the offspring brain that regulate metabolism and communication with the gut. We will also evaluate how this model alters genes and cells in the gut required for growth and establishing appropriate immune defences and responses. Finally, we will test the impact of non-digestible fibres and specific microbes, delivered during key periods of growth and immune system development, on the interactions between the gut and brain and their ability to optimise development.This research takes a comparative approach and integrates environmental, host and microbial factors to identify gut-brain connections that mechanistically link growth with immune function. Defining these interactions has the potential to advance knowledge of the biology of stress resilience and compromised immune function, and impact efforts to optimise growth and establish superior immune defences in animals.