TWiV 264 letters
Cassie might want to take a look at Sönke Johnsen’s web site. Here’s a bio page. It’s also a sample of his beautiful lab web site:
> I then worked as a daycare provider and kindergarten teacher for Quakers, a freelance carpenter, and a dance teacher for three year olds.
Also, Johnson’s “Advice for potential graduate students” seems relevant:
Dear Virologist Friends,
For the record, your pediatrician friend in Cambridge, is a woman. My first name continues to create some confusion.
Secondly, LLP, the infant in the MMR onesie, published in the BMJ, was no more than 3 weeks old when that picture was taken. She has a very caring paternal uncle to thank for the wise words. As you know, MMR is not routinely given before 12 months.
Many thanks to you, your friends, and guests for sharing so generously (and reliably) your expertise and enthusiasm for micro- and cellular biology, and especially virology!
The season’s best of Comfort and Joy to all!
Your pediatrician friend in Cambridge,
PS It’s -4 C at this moment.
Johnye Ballenger, M. D., FAAP
West Cambridge Pediatric and Adolescent Medicine
Johnye also sent this:
Dear Professor TWIV team,
You will probably get many submissions of this but in case you don’t, I wanted to make you aware of “The Wrapup Project” which donates money – raised by selling wrapping paper – to help the homeless. The wrapping paper designs are made from images of influenza, the common cold, and pneumonia. Give the viral gift of the year to your loved ones this season!
PS: It is currently 28F and sunny here in Lexington, MA and looking forward to hopefully upper 70s and sunny in Florida next week.
Matt Frieman writes:
Wrapping paper design made from the EM structures of viruses. Pretty cool and proceeds to go a good cause.
I had the opportunity to hear Brian Deer, the journalist involved with exposing the Andrew Wakefield scandal, speak about the MMR controversy. When asked about science writing and educating the public about these issues, he was pessimistic about the possibility of educating an apathetic or uninterested public about issues that are increasingly complex and specialised — if a scientist can’t understand research being done in a field other than his own, how can we expect a non-scientist to understand these issues?
I thought this view seemed overly despondent, and I would be interested in the TWiV crew’s response. Is the public uninterested and apathetic about science, and does the increasing technicality of science preclude educating the public enough to make informed decisions?
Thank for your time and input,
Undergraduate biology student currently in Oxford
Dear Vincent, Dickson, Alan, Rich and Kathy,
After hearing on TWIV 255 a mention to the two recent Science papers about the antiviral role of RNAi in mammals, I was delighted to find that you chose both papers to be commented in the last TWIV: indeed, this gives me the opportunity to send a follow up.
I had the chance to attend an EMBO workshop last month in southern France, where Shou Wei Ding and Olivier Voinnet (the two senior authors of these studies) explained their findings in front of an audience of mainly plant virologists, generating a vivid debate. As you know, RNAi mechanisms were discovered almost simultaneously in C. elegans and in plants, and since those early works, plant virology has been contributing with a pile of evidence of its antiviral role in plants RNA silencing suppressors (RSSs) in virtually all plant viruses studied so far corroborates this (incidentally, both Ding and Voinnet were co-authors in one the very first papers finding RSSs in plant viruses, back in 1998, Viral pathogenicity determinants are suppressors of transgene silencing in Nicotiana benthamiana. Brigneti G, Voinnet O, Li WX, Ji LH, Ding SW, Baulcombe DC. EMBO J. 1998 Nov 16;17(22):6739-46).
I really enjoyed your dissection of these two studies, and the insights you bring up to the surface. For plant virologists there are many subtleties to discover in the relationship of viruses with animal hosts, that makes me wish a more fluent communication between plant virology and animal virology that would be truly enriching for both. As a particular example, the suggestion that insect viruses (like Nodamura virus) could provide a sort of bridge for functional evolution as they are able to infect different hosts might apply as well for plant viruses. In fact, a remarkable proportion of plant viruses are transmitted by insect vectors (for a review, see: Status and prospects of plant virus control through interference with vector transmission. Bragard C, Caciagli P, Lemaire O, Lopez-Moya JJ, MacFarlane S, Peters D, Susi P, Torrance L. Annu Rev Phytopathol. 2013;51:177-201).
Thanks once again for sharing your time so generously. Episode 256 with your whole crew o ent.
With my best regards,
[PS: Another very nice fragment of the last episode was your thoughts after reading Bekah's letter, including the wonderful story of Dickson's Spanish teacher. Just a suggestion for Bekah: she can check out a divulgative podcast in Spanish, from the public broadcasting service in Spain: "Entre probetas" (it translates something like "Between test tubes") https://itunes.apple.com/es/podcast/entre-probetas/id301720785 . The episodes are short (only a few minutes), but they are uploaded quite frequently.
Finally, please be reassured by an avid podcast listener during my daily commute that indeed no other science podcast can be compared in tainment with the TWIx series: I strongly endorse Vincent's claim]
Loved the rant in MTor. The details are fun.
Would it be possible to list the next week’s papers in the the current week’s show’s notes. A site where they might be found would also be helpful. Not sure I will do them all but could help to rid me of tv.
Hedgehogs are an old world mammal, with species found throughout Eurasia and Africa. Their import into North America is banned.
With frequent reference to taxonomic trees, TWIV should assign a new office of Branch Manager. I nominate Dr. Alan Dove who would be good at managing the public relations implications.
I love hedgehogs but haven’t seen any since I left the Old World, in spite of returning to that area for one+ year in Ouijongbu and half a year in BushDaddy’s war.
Audios are *.mp3 and videos are *.mp4 (some emailer was going to record a mp3 from a video).
Why shouldn’t vaccine strains of polio be added to Coke™, Pepsi™, beer, bottled water, etc? Will be easier to distribute in the endemic areas. Better than gulping crappy strains from crap?
Good morning TWiV team!
I wanted to thank you for reading my last e-mail on TWiV 256 and for your discussions on how modern medicine might affect evolution. You brought up several points that I had not previously considered. You asked when reading the e-mail where Nationwide Children’s is located. It is in Columbus, Ohio and is affiliated with The Ohio State University. And, in response to the comment of “Go Blue” at the end of the episode I am required to respond, “Go BUCKS!”
Also in this episode you mentioned two papers on miRNA and whether or not they were antiviral in mammals. I just wanted to remind you that the TWiV team has already discussed antiviral miRNA a couple of times on TWiV and even picked the discussion with Dr. Coyne at ASV as a story of the year at the end of 2012. This paper/story from Dr. Coyne’s lab was the one concerning primary human trophoblast cells, where miRNA within exosomes conferred protection to other cells through induction of autophagy. I believe that this would meet the parameters set forth on this episode, though I have not yet read the review article you suggested.
P.S. It is currently 10C with 57% humidity, winds at 7 mph out of the southeast and completely overcast here in Columbus, Ohio.
Graduate Research Associate
I’m an undergraduate student at Colorado State University, and would love to hear about this concept. The video talks about “reprogramming CD8 T-cells” to attack/ kill leukemia cancer cells. How does this work? What is the actual success rate? Could it be used to treat other cancers?
Hello Twiv gang.
Just another story with Jenny McCarthy.
I’ve Got Whooping Cough. Thanks a Lot, Jenny McCarthy.
Dear TWiV Crew,
As a long-time listener, I have always wanted to write in and share my appreciation and compliments for the TWiV podcast. I have spent countless hours listening and learning while in the culture hood and setting up PCR reactions. Thank you for all that you do to bring science and technology together!
I am also writing to share a new science podcast that a couple of other graduate students and I have started called The Petri Dish Podcast! We wanted a way to become more informed and up-to-date with major topics in science, while providing information in a fun way for anyone with an interest in science. We hope to encourage listeners to ask more questions and initiate conversations of their own.
We recently released our first episodes of The Petri Dish Podcast on iTunes and are excited to share with a larger audience.
We’ve received some positive feedback but are looking for ways to become more visible and continue improving. We would welcome thoughts and any insights you and your team could offer to new podcasters. Please let us know what you think!
Lastly, if possible (and to get the famous TWiV bump) we were hoping you might consider our podcast as a listener pick of the week. Regardless, any advice or feedback would be most welcomed and greatly appreciated!
Lindsey and fellow Petri Dish hosts Rachel and Sabriya
The Petri Dish Podcast links and contact information:
Facebook page: https://www.facebook.com/thepetridishpodcast
Dear TWIV team,
First time e-mailer long time listener (since around episode #15).
Thought this might be of interest:
PS: I know it has been a while since it aired but I wanted to mention that TWIV#146 certainly was a joy to listen to as I work at MIT Lincoln Laboratory and had no idea that we had a group working on such things (considering the Lab was started in the 50′s to develop advanced electronics for air defense it has certainly branched out).
Radiolab (I know, I know) did this (link) 30 minute presentation about rabies and the use of induced comas to save lives. I’ve been bothered by the fact that rabies is transmitted via saliva, but travels along the nerves to the brain. I thought the neuronal pathway protected the virus from any immune response. If the virus is in the saliva, a response should occur and presumably both the immune reaction and protected path usually occur at the same time. However the antibodies cannot pass the blood-brain barrier to block the virus when it arrives there. Is this right? If so, then is it correct to assume that comas are not a factor in saving a life by slowing down brain activity until antibodies build up sufficient numbers to neutralize the virus?
I mentioned Dickson in the Subject line because another podcast, AAAS Science Magazine (link) includes comments about Plasmodium vivax malaria becoming more important as progress is made at removing P. falciparum from the environment. (Link to that topic’s summary. Full transcript requires membership.) The discussion also mentions that at one time the Nobel Prize was awarded for the use of P. falciparum to cure syphilis, much the way comas have been applied to rabies cases. I wonder what the protestors of bad science or bad research would make of each example.
Matthias Schnell answers:
First I do not want to get much into rabies virus (RABV) treatment – the so called Milwaukee protocol – except that is highly controversial – in my opinion there is no treatment for rabies after onset of rabies symptoms. In rare circumstances people do survive rabies but the chances are very very low!
Now to the question – yes its true rabies stay “under the radar” of the immune system and reaches the brain via motoneurons and it is not detected by the immune response of the host. The brain is a immune privileged site so with any “signals” that something is going wrong no immune cells enter so no immune response. So that is the problem.
The listeners now want to know if RABV is immunogenic when it reaches the salivary glands. Probably yes. However that is already to late (last step in the life cycle of the virus). In addition people in the later stages of the disease do have sometimes good amounts of antibodies against RABV – again its to late the damage to the CNS is done. This is the problem with RABV – when symptoms occur there is already a lot of the brain infected.
In addition it has been tried to vaccinate people after symptoms of rabies occurred but without any success to save them. Now some research groups analyze if you need a certain kind of antibodies (Ig1 versus Ig2). Again the problem remains that when you have symptoms of rabies the virus did already the damage.
So after a potential exposure get your vaccine and you will be fine its 100% effective.
Hope that helps
Dear Dr Racaniello & friends,
If you ever have a scientist/pollster on the show, would you mind asking them a few questions? Not super pressing, but if there’s an awkward lull and you need to fill the void, I’d be grateful.
Here’s what I’d _love_ to know:
% of people who believe viruses are bacteria.
% of people who believe antibacterials can treat viral infections.
% of people who believe antivirals can treat bacterial infections.
I have plenty of poll results that talk about “% believing that antibiotics can treat viral infections”, and the above data would be all the different misconceptions to be factored separately (i.e., there is confusion over definition of “antibiotics” as well as confusion over taxonomy of viruses).
I’ve asked approximately 20 people (and Pew) if they have data on the above, and nobody does. You are my last hope.
Thanks very much for your time.
Just listening to TWiV 258 while working alone in the lab at night. Vincent was wondering about the typhoon in the Philippines – known as “Super typhoon Haiyan”. I submit my listener pick of the week for some perspective on this monster of a storm. It’s a post from Phil Plait’s “Bad Astronomy” blog showing two pics of the storm from space – one from 700 km (430 miles) up, and another from 36,000 km (22,000 miles) above the Earth’s surface. A perfect example of how nature can be simultaneously beautiful and terrifying (something I don’t have to tell to a bunch of virologists).
News from Masschusetts
Hinton State Lab Identifies New Strain of Influenza
Scientists at DPH’s Hinton State Laboratory Institute have identified a new strain of influenza which was one of the four strains included in the development of the 2013-14 influenza vaccine. “The Hinton Lab is the first state laboratory in the nation to successfully identify a new strain for the Centers for Disease Control and Prevention (CDC), which named the strain “influenza B/Massachusetts/2/2012-like virus” in recognition of the finding.
Each year, the CDC looks to state health laboratories to help identify what strains of influenza are circulating at the local level across the United States. This information is provided by the CDC to the World Health Organization (WHO), which convenes a group of expert scientists from around the globe to decide which strains to include in the flu vaccine manufactured for the upcoming flu season.
“The Hinton State Laboratory Institute is proud to have played an integral role in the formulation for the most effective vaccine possible against the flu,” said Hinton Lab Director Michael Pentella, Ph.D. “This recognition is a testament to the hard work of our scientists and researchers who focus on the health and well-being of all Massachusetts residents.”
Johnye Ballenger, M. D., FAAP
West Cambridge Pediatric and Adolescent Medicine
More positive survival data out of Amgen’s phase 3 with oncolytic herpes virus:
I just listened to you caveat mTOR episode (I feel like there’s a joke in that title I’m missing) and I thought you might be interested to know that mTOR is also a hugely important molecule in neuroscience. It is down stream of BDNF signalling, which has been implicated in pretty much every psychiatric or neurodegenerative disorder. A quick Google-scholaring didn’t turn up any role of BDNF in peripheral immunology, so maybe the immune-privileged nature of the brain allows mTOR to have this dual role? Either way It’s interesting that mTOR would have such different effects centrally and peripherally, or I guess it could be having overlapping but uncharacterized functions in both places.
This also seems like a good opportunity to suggest a somewhat self-serving listener pick of the week: You may remember that a while ago I emailed you asking for podcasting advice. I’m happy to report that my TWiV-inspired neuroscience podcast – On Your Mind – is now up and running. So if any of your listeners, or any of you for that matter, would like to learn more about neuroscience or life as a graduate student I would encourage you to check us out (www.OnYourMind.ca).
Thanks again for your help and inspiration,
Dear Vincent & friends,
I really like your podcast. Thank you for your fantastic work and teaching us so much over the years. Keep on with the good work.
I work in influenza A virus assembly mechanisms in Instituto Gulbenkian de Ciência in Portugal, which is a fantastic place to do research. The institute accommodates a strong but quite broad research community, being a perfect place to establish multidisciplinary projects and collaborations.
In this sense I was talking to a friend a colleague at work about one of my favorite aspects of viral assembly, which is the ability of this virus to adopt different forms: filamentous and spherical (determined by several viral proteins being the most prominent M1 and M2). To refer this characteristic, I told her that the virus is pleomorphic (or pleiomorphic, I never know), which is what we read in papers (and to the best of my knowledge we don’t use polymorphic). She asked me why we called this feature a pleomorphism rather than a polymorphism and I couldn’t provide a satisfactory answer. Any virus is pleomorphic because it has different shapes during its lifecycle: virion versus inside a cell, maybe even when budding. But in this context we actually mean the different forms strains may adopt as a virion. So I have decided to ask your opinion regarding this matter and hope you can actually inform us on why we favor the usage of pleomorphic rather than polymorphic.
Thanks a lot,
First, why did Alan fail to point out that you reached a great milestone in binary, 2^8 episodes?
Second, since this is a virology podcast rather than zoology it is important to explicitly mention a limitation on Gould’s theory of evolution.
Gould restricts some of his statements to sexually reproducing metazoa. Obligate sexual reproduction forces a huge amount of gene mixing which makes speciation almost impossible. To overcome the inertia of the established genome requires an extraordinary fitness advantage or a severe drop in population size (by population reduction or reproductive isolation). So we see punctuated equilibrium.
Some animals reproduce asexually, and have no mixing. They need not follow the same pattern.
Prokaryotes and viruses are somewhere in the middle. They normally create clones, exact copies except for errors, but they can exchange genes with closely or distantly related species. They could follow a third pattern of evolution, not the same as sexually or asexually reproducing animals. Perhaps they are closer to plants.
If you want to nitpick, retroviruses enable horizontal gene transfer in animals, but this does not seem to be a common cause of speciation.
Interesting reading on mathematical models of evolution, but probably inapplicable to viruses:
Martin A. Nowak. Evolutionary Dynamics: Exploring the equations of life. Harvard University Press (http://www.hup.harvard.edu/catalog.php?isbn=9780674023383)
Can someone clarify me that why in vaccine potency testing challenge dose of 10000 ID 50 is used? why not 100 ID50 or 1000 ID50 or 1,00,000 ID50? what determines this challenge dose for the vaccine to be passed to public use after manufacture?
I listened to your video on this topic, and it really intrigued to look into this topic some more. And, I have a question which has been bothering me for some time… How does cGAS differentiates between self DNA and foreign DNA, and if we can, then how and why we can use it against autoimmune diseases?
Your thoughts on this would be highly appreciated.
Dear Vincent et al,
Hello, I am a graduate student in RU. I sometimes pick up past TWiV randomly and listen to them. I was surprised to hear that there are very high-resolution Cryo-EM structure of virus. This time I am writing with a small question.
You know recently there are many high-resolution Cryo-EM structure of viruses, say, 3.5 A structure of dengue virus or 3.2 A structure of aquareovirus. Then I have just come up with an idea. If I could transform a membrane protein which is originated from other species (say GPCR from human) to the surface of the virus membrane, and if that transformed virus is stable, we can try Cryo-EM with that transformed virus and get the structure. Then we also can get the structure of transformed protein.
You know it is very difficult to overexpress, purify, and crystallize membrane protein but in this way these difficulty could be overcome.
This is just an idea and I would greatly appreciate if you guys can give me some comments!
Thank you for always giving me interesting talks!
I had a question pertaining to Dr. Dudley’s research on the Rem signal peptide of the MMTV. Both on the podcast and in the literature, it was mentioned the Rem peptide, in order to be functional, must enter the ER and have its signal peptide cleaved, after it enters the ER, it is then pulled out by the misfolded protein surveillance machinery, and is then localized to the nucleus where it serves as both a NES and NIS.
Since you mentioned it was pulled out by machinery which searches for misfolded proteins, I was curious if you know how the protein avoids ubiquitination after being removed from the ER?
Jackie Dudley responds:
Shawn asks an excellent question, and we do not know the exact answer. To clarify, Rem has an unusual signal peptide (SP) with both NLS and NES motifs for nuclear function and RNA binding. The signal peptide directs Rem translation to the ER membrane. Nevertheless, Rem function requires SP cleavage from the Rem precursor using signal peptidase, which is located in the ER lumen. After Rem cleavage, the peptide can be extracted from the ER membrane using the ER-associated degradation (ERAD) process. ERAD is crucial to avoid overloading the cells with misfolded or misassembled proteins, such as in Alzheimer’s disease. SP extraction from the ER membrane requires the AAA ATPase p97, which is part of the retrotranslocon (a channel in the ER membrane). Usually proteins are identified for retrotranslocation and proteasome degradation (the ERAD process) by modification of a target protein with chains of the ubiquitin peptide. We have not been able to detect ubiquitin chains on Rem SP. We also expressed Rem in a cell line that is defective in part of the pathway needed for ubiquitination, and Rem is processed and functions normally in these cells. These results suggest that Rem SP is retrotranslocated in a ubiquitin-independent manner. We now have a collaboration with a lab that studies how polypeptides are identified for degradation by the proteasome. They are testing whether Rem lacks a “handle” or sequence that the proteasome uses to grab prior to routing them into the enzymatic chamber where they can be degraded. Lack of this “handle” may allow Rem to avoid degradation.
I know the twiv-ites like these bio photos….. here are some more…
ps Happy holidays
I;m in San Diego Dec 16th 71 degrees f, 22 degrees C, Sunny, 19% humidity, 2 MPH winds.
You guys are in snow, 31 degrees F (0 degrees C), 43% humidity – but we both have 2MPH winds…..