The main goal of my work is to understand to what extent the bacteria in the guts, or microbiome, affect the reproductive system and the health of offspring. We know that the microbiome can be easily perturbed by the diet, by drugs, ultimately by anything that we get from the environment. And, we know that such changes can affect the brain, the immune system and many other organs, but we do not know much about the effects on the reproductive system. The ultimate goal is to understand how the lifestyle of parents impacts future generations, in particular when it comes to the risk of chronic disease.
I use mice for my experiments. I start by giving antibiotics to young male mice for 6 weeks. Their microbiome becomes more or less depleted. When my collaborators and I checked their sperm cells and compared them with those from a control group, we noticed that genetic material has not changed, but the small RNAs that regulate gene expression were disrupted.
Then we have these male mice mate with healthy females. First, we check what happens during pregnancy, and we notice that the placenta has defects that make it less functional. In the end, we find that part of the offspring has either severe developmental delay, or lower birth weight, which in humans is a risk factor for chronic disease. Some of these mice die before they reach maturity.
At this point the question becomes: is it only the sperm cells that are transmitting the information, or are there other factors involved? To answer this, we take eggs from the female mice, put them in a control dish and fertilise half of them with sperm from the male treated with antibiotics, the other half with control male mice. The next stage is shown in this picture. I am using mouth pipetting to pick up the fertilized embryos and prepare them for transplant in a surrogate mother. The goal is to check whether we get the same results that we see after natural mating, and the answer is yes. This leads us to the conclusion that the phenotype we see in the offspring is really due to epigenetic information found in the sperm cells, that in turn are disrupted by damage to the microbiome.
This project was a change for me, because my background is more clinical. I got my master’s degree on infectious diseases in Ethiopia, where I was born and raised. Then I came to Italy for my PhD at the university of Rome Tor Vergata, thanks to a scholarship for international students. There I worked on human endogenous retroviruses (viral elements that have become part of the human DNA), and their role in cancers, in particular in melanoma. During my PhD I realized how little we know of the environmental factors that contribute to cancer, as opposed to genetic factors. This made me wonder about the microbiome as a possible link between the environments and the regulation of genes, so I applied to an interdisciplinary programme at EMBL, proposing to bridge epigenetics and the microbiome.
I have been in Rome for several years now and I am very happy, the people have been very welcoming. I would love to continue my career here, but it will depend on the opportunities I get. I am mostly driven by the science itself, rather than the place I work in.
