New Group Leader: Ayele Argaw Denboba

Research group investigates gut microbiota-epigenetic interaction in early life programming

September 07, 2023

Ayele Argaw Denboba is the newest group leader at Freiburg’s Max Planck Institute of Immunobiology and Epigenetics. He will lead an independent research group exploring microbiome-epigenome interactions in early-life programming. The Denboba lab also plans to identify the epigenetic mechanisms by which gut microbiome-mediated effects are transmitted across generations. The lab opened in August 2023 and has exciting vacancies.

Trillions of microbe inhabitants colonize the gut, collectively termed the microbiota. They help the host to digest food, train the immune system, influence neurological responses, or protect against pathogens. Interestingly, chemical crosstalk between the host and the microbiota regulates physiological processes in tissues and cellular metabolism. For example, changes in the gut microbiota composition are known to influence health and disease by inducing epigenetic changes such as DNA methylation or histone modifications.

Research from recent decades has highlighted how microbiota influences the cellular and molecular responses of the host somatic cells. However, whether these microbiota-epigenetic interactions can extend to germ cells or are even transmitted across generations remains an open question.

The newly established lab of Ayele Argaw Denboba at the Max Planck in Freiburg sets out to answer precisely these questions. “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 in early-life programming,” says Ayele Argaw Denboba.

Microbiota epigenome interactions in early-life programming

The Denboba lab wants to uncover the regulatory role of gut microbiota in gametogenesis and embryogenesis. The team uses a wide range of state-of-the-art approaches from the microbiome and epigenetics fields to determine whether microbiome-mediated epigenetic effects are transmitted across generations. “To do this, we aim to identify gut microbes and their metabolic products that regulate chromatin functions in early-life programming,” explains Ayele Argaw Denboba.

Beyond a better mechanistic understanding of the associations between microbiota composition and epigenetic modifications for regulating germ cells, the research enriches the field of reproductive biology. Thus, it could represent a new avenue for developing predictive diagnostic markers for adverse pregnancy outcomes and formulating microbial supplements to prevent health risks across generations.



Interview with Ayele Argaw Denboba: Six questions for the new group leader of the MPI-IE

Hello Ayele, welcome to the MPI here in Freiburg, and we would like to learn more about you and your research. What is your work area, and how has it evolved over the last few years?

My lab will explore gut microbiota-epigenetic interaction in early life programming (i.e. oogenesis and embryogenesis), and identify microbiome-sourced metabolites that regulate chromatin functions. This project stems from my postdoc research, which sought to understand the impact of gut microbiota on the male germline and the subsequent intergenerational effect on their offspring. In this study we revealed previously unknown intergenerational mechanisms that propagate through the gut-germline-placenta axis.

Your research proposes to bridge epigenetics and microbiome. Please tell us more about the questions your lab is trying to answer.

Gut microbiota plays an important role in regulating host physiology and operates at the interface of host-environment interactions, but their impact on epigenetic inheritance and early life programming remains largely unexplored. My lab aims to answer the following key questions.

  • 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.

The topics are pretty diverse: the gut microbiome, chromatin regulation, epigenetic inheritance, and chronic disease. When did you first become interested in these topics and their synthesis?

During my PhD, I studied how abnormally activated retrotransposons play a role during cancer progression. Working on this project, I learned the complex features of cancer onset and progression, and the numerous efforts made to cure cancer patients with often unsatisfactory results. Over time, I became interested in factors that influence cancer development beyond genetics, which led me to realize early-onset cancer incidence is increasing in successive generations. Noteworthy, other chronic diseases follow a similar trend and are largely not explained by genetic risk factors. This marked a change in my research interests from studying malignant tumors to exploring intergenerational modifiable health risk factors.

It was this understanding that led me to develop a postdoctoral project at the interface of epigenetic inheritance and microbiota, aimed at establishing a link between the parental gut microbiome-germline interaction and offspring health. In 2018, I initiated this interdisciplinary postdoctoral project under the supervision of Dr. Jamie Hackett (EMBL Rome) and Prof. Dr. Peer Bork (EMBL Heidelberg), which was co-funded through the EMBL-Marie Curie Action EIPOD fellowship programme.

What technologies do you use to answer your research questions? And which model organisms do you use to study these questions?

To address key research questions, we will apply the latest tools and techniques from both the microbiome and epigenetics fields. Our approach integrates high-throughput cell-culture systems and mouse models with cutting-edge culturomics and multiomics at bulk and single cell resolution. Particularly, we will use germ-free mice, which enables the lab to study epigenetic programming under different gut microbial states, such as monocolonization with specific bacteria species (e.g. methyl & acetyl donors).

On a more personal note, what inspired you to become a scientist?

Since childhood, I have been passionate about finding solutions to problems and helping others. During my high school years, I was fascinated by evolution and genetic engineering, but reading the story of Dolly the sheep, the first mammal to be successfully cloned from adult cell, greatly inspired me to become a scientist. Despite my desire to become a scientist, I was not sure what career path to pursue until I joined medical school. Being raised in Africa and attending medical school has given me an in-depth insight into chronic diseases and the poor quality of life patients experience. It is this first-hand knowledge that has shaped my scientific interests and inspired me to explore the underlying causes of chronic disease susceptibility.

Finally, tell us an interesting fact about yourself that we don't learn from your CV.

Besides my core scientific interests, I am also enthused about planetary health and artificial intelligence. As a hobby, I enjoy long distance running and biking – I am looking forward to exploring the Black Forest.


CV Ayele Argaw Denboba

Ayele Argaw Denboba, born in Ethiopia, studied clinical laboratory science and tropical & infectious disease at the University of Addis Ababa in Ethiopia. He completed his Ph.D. at the University of Rome “Tor Vergata” in Italy with a project investigating the role of retrotransposons in cancer progression. From 2015, he was a postdoctoral research associate at the University of Rome “Tor Vergata” and then became a Fellow in the international flagship postdoctoral program EI3POD at the European Molecular Biology Laboratory (EMBL) in Rome, Italy, in collaboration with EMBL Heidelberg, Germany. His postdoctoral research focused on gut microbiota-germline interactions.

Since August 2023, Ayele Argaw Denboba leads the research group “Microbiome-Epigenome Axis in Early Life Programming” at the MPI of Immunobiology and Epigenetics in Freiburg (MPI-IE), Germany.


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