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Researching on
Researching on
Why does it feel better after sports, workouts, running, biking, hiking, or even romance? All these activities temporarily limit the oxygen supply (benign breathlessness) and thus deliver an intermittent hypoxia. We found that the Hypoxia Inducible Factors (HIF1a) respond to the hypoxia by activating a family of human endogenous retroviruses (HERV), a remnant of ancient retroviral invasions in our genome. In turn, these HERVs with enormous regulatory potential, re-wire our cellular homeostasis in myriad ways. Notably, HIFA and this HERV are downregulated in multiple brain disorders e.g., major depression. Indeed, our upcoming paper shows that the patients gradually recover from depression, anxiety and OCD from being in a hypoxia chamber for 3 hours every day, for 4 weeks. The precise mechanism, at molecular level, however, is unknown which we are after.
Survival of human embryos relies on the remnant of ancient retroviral infections
Survival of human embryos relies on the remnant of ancient retroviral infections
In the earliest stages, three days after fertilization, there comes a storm of global activation of DNA. Plenty of transposons that can hop around and cause DNA damage are also activated at this stage. If this storm of DNA damage caused by jumping transposons is not stopped immediately then every single cell of the human embryo is destined to die and thus the embryo is likely to perish. The next day, the beginning of day 5 of the embryo is the most crucial stage because the most potent cells called pluripotent cells have to be defined which will further make up all the other types of cells in the human body. How the events that take place on day 4 determine whether the embryo shall live or die.
We noticed a new group of cells that had not been seen before. The existence of this cell population could have been overlooked because of the death of these cells. We found these cells using the deep learning algorithms on the datasets. Later, they validated the existence of these cells using in-vitro fertilized embryos in different laboratories from Spain and the United Kingdom. These cells were non-committed: they did not become a part of the later stages of the embryo. They seemed to get eliminated early on in development, compared to the pluripotent cells, which went on to make the developing embryo. In a 2014 study from Dr. Izsvak’s lab, we showed that human pluripotent cells are marked by retroviral sequences known as human endogenous retroviruses (HERVs). Most of the embryonic pluripotent cells express HERVH – but not the non-committed cells that eventually die. Through a series of experiments, we found that HERVH ends up protecting the cells from the damage inflicted by the jumping genes, kickstarting a protective mechanism that prevents the transposons from getting expressed in most cells. But some cells – the non-committed ones – don’t express HERVH and are killed off by the uncontrolled transposon activity. This is the classical example of survival of fitness after the struggle of existence which starts in human life even before the embryo has implanted in the mother’s womb. This finding opens an avenue to find the cause of infertility and of developmentally challenged children.
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