Laboratory Ayele Argaw-Denboba
Microbiome-epigenome axis in early life programming
Gut microbiota provides an ideal interface for studying host-environment interactions. In the past decade, there has been tremendous interest and progress in understanding how altered microbiome (dysbiosis) influences the cellular and molecular responses of host somatic cells. However, whether this effect extends to modulating epigenetic programming in germ cells (gametogenesis) and during development remains an open question.
Epigenetic regulators in every cell requires appropriate substrates and cofactors to modify chromatin structure and functions. Gut microbiota produces a myriad of biomolecules, including those that act as substrates, cofactors, or regulators of epigenetic enzyme activities. Nevertheless, it remains largely unexplored how gut microbiota and their metabolic products influence mammalian epigenetic mechanisms.
Major research areas of the lab include establishing a comprehensive understanding of microbiome-epigenome interactions in early life programming (i.e. oogenesis and embryogenesis), and identifying mechanisms by which gut microbiome-mediated effects are transmitted across generations. We are also interested in exploring gut bacteria that produce metabolites that feed into one-carbon (1C) metabolism pathways. 1C metabolism is directly linked to chromatin modifications, and plays a crucial role in development and metabolism.
We aim to accomplish the following four goals to gain insight into the microbiome-epigenome interactions in early life programming:
- Decipher the regulatory role of gut microbiota during gametogenesis
- Determine the impact of parental gut dysbiosis on epigenetic inheritance
- Identify gut microbes and their metabolic products that regulate chromatin function
- Develop a high-throughput screening platform to predict the cellular and molecular targets of microbiota-sourced metabolites
To tackle our research questions, we leverage both established and emerging technologies used for epigenetics and microbiome research. Our approach integrates high-throughput cell-culture systems and mouse models with cutting-edge culturomics and multiomics at bulk and single cell resolution. Furthermore, we evaluate and validate the regulatory role of specific gut bacteria species (e.g. methyl & acetyl donors) using germ-free mice.
Insights gained from our research will open new avenues for discovering probiotics and prebiotics that can regulate or maintain epigenetic enzyme activities at the local or systemic level. Our research will also have a wide range of implications in reproductive biology and translational research, enabling the development of predictive diagnostic biomarkers for adverse pregnancy outcomes and formulation of preventive microbial supplements that mitigate intergenerational health risks.