Vincent and Nels,
I really enjoyed the most recent TWIEVO on the importance of DHX9 in defense against endogenous Alu RNA, and particularly the appearance of ADAR, given recent interested of our lab. It’s been known for some time that genetic ablation of ADAR is lethal to mice at the embryonic stage, but that this could be overcome through ablation of MDA5 or MAVS (though these mice still aren’t exactly healthy).
Recently, we discovered we couldn’t even knock out ADAR in human A549 cells. We had previously found that RNase L activation is the primary mechanism of cell death after introduction of polyIC and decided to test if RNase L ablation would allow us to knock out ADAR. Unlike most experiments, it worked, and was published earlier this year in eLife.
We did a few other things to really nail down that RNase L was responsible for the lethality observed in the absence of ADAR. Specifically, we made a cell line expressing the NS2 protein of mouse hepatitis virus, a well characterized antagonist of RNase L. In this cell line, but not a cell line expressing a mutated, inactive NS2, we also successfully knocked out ADAR. Additionally, we determined that cells lacking ADAR produce more 2-5A, a small molecule required for RNase L to activate.
I’ll avoid going on any longer than that, but thanks for highlighting the really cool and growing field around modification and sensing of endogenous RNA, and overlap with antiviral responses. Thanks as well for making TWIEVO happen, and it’s been a pleasure meeting both of you over the last several months.
The question of the advantage(s) of size came up on TWiEVO 26. Here are some impressions/speculations:
1) The ability to support a bigger brain. That appears to be the reason for the increase in size in hominids.
2) Due to the vastly reduced surface area (proportionally), gigantic animals will cool much more slowly — clearly an advantage for the whales that inhabit very cold water. Might this have been an advantage for for the dinosaurs, too?
3) Taller animals can graze on trees and see food/water/predators that are far away.
Might the large size — and blubber — of the sperm whale enable the deep water dives necessary to hunt the giant squid?
There was mention of reduced predation. This could quickly result in an arms race that produces all giant animals — predators and prey alike.
Vinny Lynch responds:
I think there are probably lots of reason being big is both good and bad. Whether a species evolves to gigantic sizes probably has to do with how those advantages and disadvantages are balanced in that particular lineage. Being big is great but it takes a long time to grow big, time in which reproduction isn’t happening so if you die before you reach maturity there’s not much help there!
I’d bet there is probably an upper limit to predator size. All the really big things are or have been herbivores. My guess is that it’d hard for super gigantic predators to get regular access to food or something similar. But being big is definitely a good way to stay warm!
Vincent J. Lynch, Ph.D.
Department of Human Genetics
Department of Organismal Biology & Anatomy
The University of Chicago
James Joyce’s Pouter Pigeon simile in Ulysses
Joyce clearly demonstrates that he was familiar with the appearance of Pouter Pigeons. I wondered how that came to be? When young, did he or an associate keep pigeons? Did Joyce browse the live animal markets? I also wondered why he used an image that few would likely recognize. A Joycean gave me a likely answer to both questions. In Joyce’s era every educated person would have studied Darwin and would have been familiar with his experiments in atavistic reversion in pigeon crosses.
# # #
BLOOM: Yes, ma’am?
MARION: TI TREMA UN POCO IL CUORE?
(IN DISDAIN SHE SAUNTERS AWAY, PLUMP AS A PAMPERED POUTER PIGEON, HUMMING THE DUET FROM Don Giovanni.)
BLOOM: Are you sure about that VOGLIO? I mean the pronunciati …
Dear Nels and Vincent,
It is currently in the 43ºF (6ºC) in Durham, NC, but since I am almost always in the greenhouse, it is perpetually in the 70sºF/20sºC. Working in the greenhouse has meant a lot of time to listen to podcasts, including TWiEVO.
I have a few comments/suggestions/questions, which I will list below:
1) I particularly loved the episodes with Corrie and Josh, who highlight the importance of natural history museums. Thank you for bringing them to light, especially since a lot of these museums are closing down.
2) I also like how several of the guests have emphasized the importance of having a question(s) to drive their research. Even though sequencing and functional genetics is becoming more accessible, it still takes a lot of time, money, and other resources to develop tools to do some functional work. It is also sometimes also hard to do with certain species, and it is worth asking whether doing the “functional experiment” like knocking out a gene using CRISPR will tell us anything new or important.
3) Coming from the perspective of a budding plant evolutionary biologist, my question is: where are the plants?? You’ve covered research from a myriad of species, and while there have been some mentions of plants, I keep wondering when plants can be the focus of the conversation. Perhaps this is in the works. If you are interested, I would be happy to suggest a few papers and people who would be fantastic guests.
4) However, if plants aren’t really in the pipeline for the future, may I recommend two plant-related podcasts as my “listener picks”:
– In Defense of Plants is hosted by PhD Candidate Matt Candeias, and his goal is to cure plant blindness. (Side note: I have no clue how he is doing this and working on his PhD – I can barely find time to do my own research.) There is a blog, a podcast, and a video series. I haven’t looked through everything, but everything looks fantastic. I have listened to a few of the recent podcast episodes, in which he talks to scientists, landscape architects, horticulturalists, etc. I think this one is similar to the format of TWiEVO and is worth a listen.
– The Taproot tells the story behind a plant-related paper – the collaborations, the challenges, the compromises, etc. It feels like a shorter version of TWiEVO, focusing not necessarily on the science in the paper, but the process of making the discoveries and getting the work published. The first episode is actually quite fascinating.
5) Finally, having heard some “panel” discussions and how some podcast taping occurs at meetings, I was wondering, would it be possible to have a TWiEVO taping at a future Evolution conference, perhaps in 2019? I only say 2019 because the 2018 meeting will be a joint meeting and that meeting tends to be very structured. Or perhaps there could be a “recap” of talks you attended, kind of like All Songs Considered recapping SXSW. It is also likely that you do recaps already in your other podcasts, but I thought I should share the idea anyway.
Thanks for all you do! I look forward to future episodes!