Can I tell you a quick cool story I learned today in a talk by Mikala Egeblad? If yes, continue reading. If no, stop – but I sure hope you’ll stay because it involves cells shooting out DNA! (and the role in coronavirus this might play!)
You have a lot of DNA (~2m per genome copy) so it has to get wound up super tightly around proteins called histones in order to store it. And you have a full genomes-worth of DNA in each cell in your body, including in a type of immune cell called neutrophils. These are more “generic”-acting that the B cells we talked about that rely on antibodies. Instead, neutrophils rely on inflammatory signals like cytokines which recruit them to come surround and trap invaders – *literally* trap them! When they get a certain signal, the neutrophils “cut the ties” keeping the DNA wound (modify the histones with charge that makes them repel each other) and, well, physics takes over! Constraints removed, the DNA shoots out kinda like one of those party poppers. Instead of confetti, the Neutrophil Extracellular Traps (NETs) are made up of the DNA and associated proteins. These NETs trap the invaders (bacteria, viruses, etc.) and some of the associated proteins have antimicrobial properties that degrade them. So all that’s really good. But sometimes neutrophils can get a little overzealous and you can get an immune overreaction and excess NET-casting. And they can trap blood platelets, which might be associated with the clotting problems observed in patients with severe COVID-19.
Researchers are hoping that using drugs to degrade NETs (such as DNAses (DNA cutters) and/or using drugs to prevent the NETs from being cast in the first place might help these patients. And there are currently numerous clinical trials underway, including ones associated with an amazing scientist at CSHL whom I had the pleasure of taking courses from, Dr. Mikala Egeblad, who has been instrumental in the effort. https://bit.ly/3fbRCc3
Mikala had been studying the role of NETs in cancer metastasis (she’s a major leader in this field) and then – coronavirus… Trying to focus on writing a cancer research grant while our region was inundated with COVID-19 and was quite a challenge. Being “distracted” had a silver lining because she realized that NETs and covid might actually be related. She remembered that NETs had been associated with Acute Respiratory Distress Syndrome (ARDS) – a compilation of severe lung symptoms that can be caused by multiple things including COVID-19. She wondered if NETs might be involved in COVID-19 so she got in contact with local hospitals and was able to obtain lung samples from coronavirus patients. And when she stained them she found… NETs!
She organized “The NETwork to Target Neutrophils in COVID-19” involving 11 biomedical researchers from around the country and they’ve been doing a lot of research. https://bit.ly/2OjnpMF
Some has to do with the basic biology of how NETs form and what role they play in the disease – among other things, they’ve found that patients with worse disease tend to have more NETs in their lungs (and in their blood). https://bit.ly/2ZcHxWZ
She recently won a Pershing Square Foundation Award to continue the research – congrats Mikala! She’s currently an Associate Professor here at CSHL and I really hope she gets Full Professor soon but I have no idea how that works – but I’m rooting for her! In addition to an amazing scientist, she’s an amazing mentor and was nominated for the CSHL Women in Science and Engineering (WiSE) group’s faculty mentor award last year.
I got to learn about her work in a talk she gave today that’s part of this thing called “Life Science Across the Globe: A Sister Institute Seminar Series” – basically, a number of research institutions around the world are trading off weeks of hosting talks – one a research talk and one a “culture” talk. Today was CSHL’s turn. Mikala talked about NETs and then David Micklos, Executive Director of the Dolan DNA Learning Center (DNALC) gave a talk about how the DNALC provides training to teachers and students around the world, largely focused on initiatives to bring their education into underserved communities. I’m really excited about the new (and huge) facility currently under construction in Brooklyn, New York. The talks are over Zoom and they get recorded so hopefully their talks will be on the website soon https://bit.ly/38AjYKK
The talks are public and free and you can watch live each week at 9am EST. Next week, July 15, is the The University of Buenos Aires/CONICET’s turn. Alberto Kornblihtt will be giving a Science Talk entitled “Chromatin, transcription and alternative splicing in the cure of a hereditary disease” and then Andrea Gamarnik will give a Science Culture Talk: “From basic science to the battlefield of COVID-19”
more on DNA & histones: http://bit.ly/nucleicacids2
more on coronavirus: https://bit.ly/covid19bbresources