Me with doctor's cap and polar bear. Photo by Lars Nilse.

People who know me well and in person, friends, family, colleagues, my boss, always looked at me in disbelief. "What? There is no Gene of the Week article on Bsx???" They are astonished because Bsx is the gene that has been with me, or- sometimes even more so – has been following me, for several years. Even if originally this wasn't planned at all, the Bsx gene was holding so many previously unknown functions for me to discover that I ultimately filled most of my doctoral thesis by researching and describing these functions. In other words: I owe this awesome hat (photo) mostly to the Bsx gene. But let’s start at the beginning.

The abbreviation Bsx stands for Brain-specific Homeobox and, as the name describes, it is only active in the brain. But what does "homeobox" mean? Well, this story is so unique that I don't want to miss the opportunity to tell you all about it.

Coronaviruses. For my part, I actually didn't know anything about them, until the beginning of this very special year 2020. And then this year everything turned upside down and by now you have probably all heard enough of the latest coronavirus strain, SARS-CoV2. For those of you who spent the last months on Mars: SARS-CoV2 is the third strain of coronaviruses that recently expanded its range of host animals successfully to include humans and in this new host, us, can trigger serious respiratory diseases. The first two coronaviruses to “achieve” this were SARS-CoV, which triggered the first pandemic of the 21st century in 2002/03, and MERS-CoV, which is around since 2012. Of these three viruses, MERS-CoV appears to be the deadliest. However, since it rarely transmits from person to person, it spreads very slowly (although there is a very real danger that this could change at some point). The first (2003) SARS-CoV in many aspects is very similar to the current SARS-CoV2. They are surrounded by a fatty shell, which is why they can be easily destroyed by soap or disinfectant. The so-called spike proteins (shown in the image in red) sit in this fatty sheath and can bind to certain proteins on cell surfaces in order to allow the virus to penetrate the host cell membranes. Both SARS coronaviruses bind with their spike protein to the same surface proteins on our cells: ACE2 and TMPRSS2, whereby – after a few rounds of mutations - the new SARS-CoV2 binds to ACE2 with 10-20-fold higher affinity than the original SARS-Virus did. This contributes significantly to the new SARS-CoV2 being so particularly infectious. Both ACE2 and TMPRSS2 thus are currently being researched intensively. This is done primarily with regard to possible therapies that could target these proteins. In this article I will introduce you to the ACE2 protein, next week I will present you TMPRSS2.

Thank you very much for your keen interest in my article from last week in which I explained that SARS-CoV-2 binds to the ACE2 protein on our cell surfaces so that it can enter our cells together with ACE2 itself. Over the last few weeks you have probably read quite a few times that Covid-19 often isn't just cause an infection of the lungs, but probably affects many other tissues as well. Usually this is attributed to ACE2 being present in many other tissues. The idea behind it: all cells that carry ACE2 can be infected by SARS-CoV2. Well, today I would like to explain why it's not that simple. If we look at the viral entry process in more detail, we find that at first only a part (the S1 part) of the spike protein binds to the ACE2 receptor and then...

... nothing else happens at first! Only when a certain protease, i.e. a protein-cleaving enzyme, splits the spike protein at a very specific point and thus exposes its S2 part, does it continue from there. It is this exposed S2 part of the spike protein that allows the virus to fuse with the cell membrane of the host cell. This cleavage and the resulting activation of the spike protein is also called priming. So for a cell to get infected by SARS-CoV2, it requires to carry this special protease on its cell surface in addition to ACE2. Since this protease seems to cleave proteins only behind the amino acid serine, it was called Transmembrane Serine Protease 2, or TMPRSS2 for short.

picture modified from Goldstein Lab via flickr

Whoever read the newspaper lately, probably came across this story: the BBC has written about it, but also The Guardian and the Washington Post: there might be life now on the moon! The questions: since when? from where? and what kind? are easy to answer: since April 2019, from Earth and it's water bears or tardigrades. I still remember my biology undergrad classes: tardigrades were a highlight in them! Unfortunately, since my specialization in molecular medicine, developmental biology and genetics I had nothing to do with these maximally cute microscopic creatures. That's why I was all the happier to find more articles on tardigrades within the last couple of years. Above all, their incredible resistance to radiation was of interest. And this superpower is bestowed on tardigrades by this week's gene Dsup, damage suppressor protein. Attention: the dsup gene should not be confused with the sup gene. Because sup encoded the SUPERMAN Protein of the thale cress, or arabidopsis thaliana, probably the most important plant model organism (more on that perhaps in another article).