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Randy Schekman (HHMI & UCB) 3: How human cells secrete small RNAs in extracellular vesicles 

Science Communication Lab
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www.ibiology.org/cell-biology...
Part 1: The Secretory Pathway: How cells package and traffic proteins for export: Randy Schekman overviews the secretory pathway and reviews historical experiments that shaped our molecular understanding of this pathway.
Part 2: Genes and proteins required for secretion: Randy Schekman explains how his laboratory used baker’s yeast to uncover major proteins involved in the secretory pathway, and describes proteins involved in budding, vesicle trafficking, and vesicle fusion.
Part 3: How human cells secrete small RNAs in extracellular vesicles: Randy Schekman outlines exosome biogenesis.
Talk Overview:
In his first lecture, Dr. Randy Schekman overviews the secretory pathway and reviews historical experiments that shaped our molecular understanding of this pathway. The journey begins at the endoplasmic reticulum (ER), where proteins that engage the secretory pathway get translated. The mRNA of these proteins codes for a signal sequence that serves as a “tag” to bring the mRNA-ribosome-newly-synthesized protein to the ER for continued translation and movement of the new secretory protein across the ER membrane into the interior or lumen of the organelle. Vesicles transport the recently translated proteins to the Golgi Apparatus, where they get “packaged” and sent to their final destination.
In his second lecture, Schekman explains how his laboratory used baker’s yeast to uncover major proteins involved in the secretory pathway, and describes proteins involved in budding, vesicle trafficking, and vesicle fusion. Schekman also presents data from his laboratory that helped to identify the ER channel through which proteins enter the secretory pathway. These series of experiments show how, step by step, scientific knowledge evolves, uncovering the fundamental mechanisms to better understand human disease.
In his third lecture, Schekman outlines exosome biogenesis. Exosomes are extracellular vesicles released by the cell, and in contrast to intracellular vesicles, exosomes contain small molecules of RNA. Schekman’s laboratory characterized the RNAs contained in exosomes and showed the importance of Ybx1 protein for the recruitment of certain miRNAs into exosomes.
Speaker Biography:
Dr. Randy Schekman is a Professor in the Department of Molecular and Cell Biology, University of California, Berkeley, and an Investigator of the Howard Hughes Medical Institute. He studied the enzymology of DNA replication as a graduate student with Arthur Kornberg at Stanford University. His current interest in cellular membranes developed during a postdoctoral period with S. J. Singer at the University of California, San Diego. At Berkeley, he developed a genetic and biochemical approach to the study of eukaryotic membrane traffic.
Among his awards are the Eli Lilly Award in microbiology and immunology, the Albert Lasker Award for Basic Medical Research and the Louisa Gross Horwitz Prize. In 2013, Schekman was awarded the Nobel Prize in Medicine or Physiology jointly with Thomas Südhof and James Rothman for their contributions to understanding vesicle trafficking. Schekman is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. From 2006-2011, he was Editor-in-Chief of the Proceeding of the NAS. Currently, he is Editor-in-Chief of the open access journal eLife.
Learn more about Dr. Schekman’s research here: mcb.berkeley.edu/labs/schekman/

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27 июл 2024

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Комментарии : 158   
@SrinivashM29
@SrinivashM29 5 лет назад
Wonderful lecture, really enjoyed it. Thank you Prof. Schekman.
@rafaelescate3618
@rafaelescate3618 6 лет назад
Great Dr. Schekman, thank you
@tpf4292
@tpf4292 3 года назад
Randy's experiments are always so satisfying...
@jozsefolasz8702
@jozsefolasz8702 7 лет назад
Wonderful lectures, thank you.
@MahirSayar
@MahirSayar 3 года назад
How are these RNAs different from viruses?
@mugogrog
@mugogrog 3 года назад
RNA is just a string of nucleobases if it has its own membrane outside a cell it's called an exosome, a virus is a complex organism that use RNA and multiply using it. It's notable that exosome RNA is usually a way smaller string of nucleobases than that in a virus since the viral RNA codes for the structure of the complete virus. At least that is how I as a layman have understood it.
@Littleprinceleon
@Littleprinceleon 2 года назад
First and foremost: the proteinaceous structure of viruses (whether RNA or DNA based genome) has evolved to protect the genomic material outside the host body to enable it's spreading from one organism to another. Exosomes remain active in the body... Some of the the viral proteins enable to choose specific target cells (while with exosomes it seems to be more general) and in many viruses (such as in SARS-CoV2) a surface protein actively fuses the viral particle (virion) with the target cell. miRNA are called microRNA exactly because they are hundred time smaller than viral RNA which are denoted genomic, since they code for more genes which directly enable the replication of this genome (and ultimately the whole virus). The picture is sometimes more complex (just as it is in almost any biological process): some viruses (most notoriously the retroviruses) have inactive counterparts called vírus like particles (VLP)...which cannot spread the way viruses do. Also there are (retro-)trans-posones and other mobile genetic elements which complicate the picture for layperson....
@user-bj9cs7lm4k
@user-bj9cs7lm4k 3 года назад
Great lecture! thank you professor. from South Korea
@BioMedUSA
@BioMedUSA 4 года назад
Very lucid explanation and thought flow of the experimental progressions. My question is why were the assays done at 30 degrees C rather than 37C? At physiological temperatures, this would dramatically affect and increase membrane fluidity (at 37C vs 30C) of the exosomes and likely associated enzymatic activity.
@mememachine2586
@mememachine2586 2 года назад
I have the same question
@simonroome5858
@simonroome5858 2 года назад
Didn't understand much of that. Thumbs up anyway, lots of technical information, well presented.
@bethaniamacedo9622
@bethaniamacedo9622 4 года назад
OBRIGADA. SOU DO BRASIL E ASSISTO SUAS AULAS COM TRADUÇÃO.
@emanuele2398
@emanuele2398 6 лет назад
Thank you.
@vidyaborah8320
@vidyaborah8320 3 года назад
Thank you. Dr. S chek an.
@toutours3244
@toutours3244 6 лет назад
Nice lecture, would be better with some reading materials
@teaezra5916
@teaezra5916 4 года назад
Could our idea of viruses be completely wrong? Could viruses actually be exosomes? Has this been studied?
@amandapoyner8141
@amandapoyner8141 4 года назад
Yes. Think nano.
@Mike-vx5hw
@Mike-vx5hw 4 года назад
My thoughts exactly... I’ve found limited study on the subject that does suggests it is possible.
@belliotrungy9107
@belliotrungy9107 4 года назад
No. Viruses have been studied in many species, including bacteria and match up to historical records. While exosomes are new and exciting and some overlap in mechanisms is interesting making that leap doesn't add up.
@belliotrungy9107
@belliotrungy9107 4 года назад
@@SueSue-mp2iu I read this already from your other post. I'm not sure if you're a Russian pushing disinformation or just have no real background in biology. It's really not that exciting a paper. Interesting! But not what you think it is......
@belliotrungy9107
@belliotrungy9107 4 года назад
@@SueSue-mp2iu again I already read that one too and while exosomes as relevant intercellular communication bubbles are new and interesting they do not at all debunk the well established field of virology.
@AlphaOmega888
@AlphaOmega888 4 года назад
13:02 He's literally explaining how they made COVID-19
@trabiccolo879
@trabiccolo879 4 года назад
The only idea I have is that for RT - PCR test, RNA Exosome or RNA Virus may both trigger a Positive, in the same way.
@MyLordexe
@MyLordexe 4 года назад
yup.
@amandapoyner8141
@amandapoyner8141 4 года назад
Yes, Exosomes are apparently easily programmed to target information to any other type of cells in the human body... Like the lungs. Aggressive and fast acting cancers.
@carloc8763
@carloc8763 4 года назад
@@trabiccolo879 totally agree, that is why I am now concerned when I hear WHO officials arguing that they could take away people from they homes to stop this "virus" www.lifesitenews.com/news/tucker-carlson-rips-who-emergency-expert-for-call-to-raid-homes-remove-sick-family-members
@Mike-vx5hw
@Mike-vx5hw 4 года назад
From what I understand a “virus” is indistinguishable from an exosome...so ya, a lot of extra positive tests would quickly add up.
@bethaniamacedo9622
@bethaniamacedo9622 4 года назад
SOU PROFESSORA DA REDE ESTADUAL. NA CIDADE DE LAGOA NOVA, ESTADO DO RIO GRANDE DO NORTE. BRASIL
@trabiccolo879
@trabiccolo879 4 года назад
Can we distinguish an exosome from a virus, as an objective of RNA detection (RT - PCR) or under the Electron Microscope?
@AlphaOmega888
@AlphaOmega888 4 года назад
13:28 he seems to be explaining exactly how to engineer COVID-19
@trabiccolo879
@trabiccolo879 4 года назад
@@AlphaOmega888 how do you mean?
@skinnygumbo2700
@skinnygumbo2700 4 года назад
Of course you can distinguish an exosome from a virus! An exosome contains your own genetic material, the virus contains foreign DNA/RNA. The primers designed for RT-PCR are specific to a RNA sequence you only find in a virus.
@hermangoranov3196
@hermangoranov3196 4 года назад
​@@skinnygumbo2700 No. its not work like that. they only see simillarity of sars-cov-2 with previous sars. 80% simmilarity my ass, trash paper, even apes with human is better (Well, thats mean the primers is not credible). You better give me source/paper that already show human to human transmision on china, and how they found it or detect it. Sadly, WHO delete the paper on official site, you can found most dead link on. www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/ wjw.wuhan.gov.cn/front/web/showDetail/2020011109036
@Littleprinceleon
@Littleprinceleon 2 года назад
@@skinnygumbo2700 I appreciate the good work of your attempt at trying to spread basic knowledge in molecular biology. However, I do not think anymore that it is really worth of it. As you can see from Herman's response above: sadly even the more rational ones are deceived by sophisticated conspiracies. Only if they would take the solemnity and patience to actually understand at least the fu.ing principles of PCR: First, that one of the primer pairs can be similar or even identical to whatever sequence in whatever genome, if the other pair will not bind to that target (or bind it in some large distance from the first one), then there will be no amplification. Second, these conspirators should finally realise that the researchers used degenerate (not hundred percent homologous) primers (based on the 2003 SARS virus genome) ONLY for the very first identification steps of this new virus (later named SARS-CoV2)...but all the following PCR test use more specific primers. They should also know, that even if 90% of the primer has homology to a sequence, but it's 3' end lacks homology, than it will not be able to serve as primer for the polymerase, so again no amplification (meaning no PCR). These are the three not so trivial but basic points about primers in PCR techniques: if a paranoid layperson doesn't understand these than can be easily led astray. But this kind of attitude wouldn't fit their world views requiring global conspiracies and pseudo-science in order to fill in the enormous gaps in actual knowledge (which are not to be ashamed of since molecular biology or worldwide economics or global sociology... are topics which can be mastered only in many years as a professional or greatly understood only in one-two decades as a hobby...). So what remains for those areas of life which we know little of: Rational believes.... But again if one starts with conspiracies (however rationalized ones) (s)he will end up with disbelief in communities other then those supporting his/her stance. And those who is not capable to acknowledge that he/she has flows in some of the basic knowledge about the topic will argue round and round reinforcing only the basic bias and contributing to even more complex confusion in those with similar mentality
@numericalcode
@numericalcode Год назад
No wonder he’s a Nobel laureate
@user-uf5vk2ey7z
@user-uf5vk2ey7z 6 лет назад
Human cells
@dantethedemon9277
@dantethedemon9277 3 года назад
A VIRUS IS AN EXOSOME
@skinnygumbo2700
@skinnygumbo2700 3 года назад
Bwahahahaha.
@dantethedemon9277
@dantethedemon9277 3 года назад
@@skinnygumbo2700 what
@kdcruz75
@kdcruz75 2 года назад
This is how they know that spike protein can be weaponised...
@azu0016
@azu0016 Год назад
@@kdcruz75 As far as I know, designing an entirely new gene and being able to to predict how its protein product folds & functions for something as large as a spike protein is still way, way beyond human capacity. In microbial genetics (my area of study) we still have to purify whatever effector protein we target and study their effect via experiment, even when we know the exact gene and its exact sequence - no, you can't just look at a sequence and know what it's protein does. Similarly, you cannot say "oh I'd modify this gene by x base pairs and that will make this protein do y". Unless you're inserting an entire gene, promoter etc. with known function... which isn't the case of covid spike protein. I guess you can still brute force through random mutations + selection if you do want to "weaponize" something - which can be done in any high-school level lab since like 1960s and everyone knows it...
@lastchance8142
@lastchance8142 2 года назад
My daughter wants to be a lab rat in biological research, yet I'm the one watching all these ibiology videos. Go figure!
@homefrontforge
@homefrontforge Год назад
My daughter studied food science and while she took the organic bio classes I watched all these videos. So...same
@user-uf5vk2ey7z
@user-uf5vk2ey7z 6 лет назад
How can science bring the youth back to the old man? How can young people be brought back to the elderly? . We need to invent drugs and treatments to remove signs of aging .We need drugs and treatments to stop the aging Also . Please deliver my letter to doctors And owners of medical laboratories for treatment
@skinnygumbo2700
@skinnygumbo2700 4 года назад
Why? If we don't die, nobody can be born. Are we that selfish?
@harimari3967
@harimari3967 5 лет назад
Chinese hamster ovary cell culture having some black dot like particles in spent media..i dont know it is contamination or not..i guess it is micro vesicles or Exosomes??
@azu0016
@azu0016 Год назад
In most cases I would first assume mycoplasma or bacterial contamination, especially if you're subculturing a lot. Imo most likely bacteria, since they are the most noticable and ususally appear as black dots.
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