The Intercellular Genetic Language Is Our First Language

Last December, Alireza Fazeli held his inaugural lecture as the new Professor of Clinical Genomics and Personalized Medicine at the University of Tartu. He presented his view on the burning issue of how cells communicate with each other and why we need to know about it.

Alireza Fazeli giving professorship inaugural lecture at the University of Tartu.
Alireza Fazeli giving the inaugural professorship lecture at the University of Tartu. Image credit: Andres Tennus / UT

Prenatal communication on the cell level

Let’s look at pregnancy and its most important stage – implantation. That is when the embryo attaches itself to the wall of the uterus. The big question about that is: how the does mother’s body recognize the child’s embryo?

This is where prenatal communication comes in. This is communication on a cellular level that requires a certain communication system, or language. Language elicits a reaction from whomever receives the “message”; it is a means of influencing someone or something.

Communication on the cellular level becomes important if we try to understand how different cells – like an embryo and cell of the uterus – recognize each other.

The uterus only has around two kinds of bacteria that can live there. Compared to the lower vaginal part, it hosts almost no other species. We can say that the uterus has a “high security level” because this environment actively defends itself against other organisms.

Our body’s defense mechanisms can include: avoidance with the help of the immune system; resistance with inflammation; or tolerance (coexistence). Therefore, if the uterus had any other defense reaction to the embryo besides tolerance, the implantation on days 8-9 (see image below) couldn’t take place and the pregnancy would halt. Only after the cells on the walls of the uterus have received the message that it is indeed the embryo is it allowed to attach.

 First week of pregnancy – attachment to the wall of uterus takes place on days 8-9.
First week of pregnancy – attachment to the wall of the uterus takes place on days 8-9. Image credit: Ttrue12 / Wikimedia

The first language we speak is therefore the one between an embryo and a uterus. Without knowing that language, we couldn’t have been born. Yet the exact language of this kind of intercellular communication is not that easy to discover.

In the last years, Fazeli has tried to understand this language better. He has observed the changes in the communicating cells. The first sign of communication that he observed was that in the presence of an embryo, the gene expressions are different than when the embryo is not present. It shows that “a signal is definitely going from the embryo to the mother to make them act differently”.

The little-known functions of the “junk DNA”

The next question is: what is this signal and this language? It may have something to do with the human genomes (these have been mapped since 2003). Humans are not different from other species in the number of genes, but we differ in the amount of what is called “junk DNA”. This is 91.3% of the genes that don’t deal with creating proteins.

We understand this part of our genes better with every passing year. We know by now that they regulate thousands of different genes and can also be responsible for regulating the language between the baby and the mother.

Fazeli has found with his research team at the University of Tartu that genomic information has indeed been transferred from the embryo to the mother. Although we don’t know what happens to the transferred genomic material, the researchers have found that it is transferred through extracellular vesicles – bags carrying information from one cell to another.

So, what happens between the embryo and the mother is that cells of the embryo send these bags of genetic information to the mother’s cells. This information somehow changes the gene expression of the mother, so that the embryo will be tolerated for the implantation to take place.

 Embryo communicating with mother´s cells with extracellular vesicles through genetic information.
The embryo communicating with the mother’s cells with the help of extracellular vesicles, or bags of genetic information.

Implications from infertility to cancer

Fazeli sees the importance and wider implication of his ideas in solving different problems, such as infertility. However, it can also be a door opener for better understanding of different diseases, such as parasitic worms or even certain types of cancer.

Why? Worms often go undetected by our body’s defense mechanisms. As Fazeli puts it, they manage to camouflage themselves somehow. Another example is Ebola, a disease with numerous casualties every year. A characteristic of this virus is the fact that it’s your own body that becomes dangerous to you. The body resists the virus with inflammation to an extent that can be fatal. In this case, if the body would communicate with the disease through toleration – by just ignoring it, like fruit bats do
– we might peacefully coexist with the virus.

Fazeli and his colleagues have also shown that the same mechanism explains the functioning of prostate cancer.

Communication in ethology and biosemiotics

Using the notion of communication in a wider perspective may not be novel, but it is a promising interdisciplinary line of research. Fazeli points to Karl von Frisch (1886-1982) as the roots of this wider understanding of communication. Von Frisch is one of the founders of ethology who won a Nobel prize for research on the communication of bees.

In addition to what Fazeli said, it’s useful to point out that communication and the metaphor of language are important aspects in different fields. For example, von Frisch’s idea is in the same line of thought with the Baltic German Jakob von Uexküll (1864-1944), who is one of the founders of biosemiotics. It is a field that is also researched at the University of Tartu and looks at the communication in the whole of the living nature — including cells.

Alireza Faxeli is an active scholar who has disseminated his research through art in public galleries to video clips on YouTube, yet he leads prominent research projects and works at the forefront of his field.

Watch Alireza Fazeli’s inaugural lecture:

Mark Mets is an intern at the UT Marketing and Communication Office.

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