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Lecture 01. Introduction/What is Chemical Biology?

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I'm going to run the classes follows all have the most important announcements at the very beginning of the class so I'll be talking about stuff like what's covered on the mid-term and what's expected from your proposal Simon etc. at the very beginning so beautifully wanna show up on time job-related a seat on be prepared because most supporters stuff is going in the 1st 5 minutes OK Oh and by the way I feel free to interrupt if you have any questions OK so don't hesitate to the becomes OK so some announcements today and again announcements will come out at the very beginning of each class Obeidi assignments this week I'd like you to obtain the textbook it's available on the bookstore the big stack them when I visited last week they ran out of bullets good Irish the if they ran out of the Amazon . com has on sale in and out and you can get them delivered very quickly effect on I know for a while Amazon was selling them at some ridiculous discount so I know because as 1 of the co-authors of interest some very interested in how the selling them along those lines up as 1 of the co-authors of planning to donate the profits from the book to anyone in this classroom back to UCI for but to support research in chemistry said so I'm requiring a book that I wrote on I'm obviously aware that I'm going to profit from that profits will go back to use your OK so if you have a copy of the course reader from previous years please throw away OK it's not going to be any get immediate skillet but I've changed the material quite a bit and the textbook is significantly improves the problems a slightly different but I think it's so the figures are much better etc. editor of course was edited soak Austria for previous years is not going to carry you need to buy a copy of textbook so Natalie had as the sounds of and and and and I think that the end of the court it thank you Natalie yes so that yes they will be posted online for you so you can enjoy them and study from them etc. other the goal here is that I use your mind is 1 of the very 1st called universities to have both the lecture classes and a laboratory classic chemical biology we started these back in 2000 when I was an assistant professor and since that time we've obviously built up quite a bit in terms of our sophistication of presenting the subject and so my goal is to really bring that level too other universities around the world and around the country so anyway that's why we're doing this but it also has a benefits you as well OK and I'm so greedy assignment for 2 for the 1st week of the Chapter 1 I'm going to be covering all the material a Chapter 1 so there's nothing for you to skim through or anything like that on future chapters there will be stuff that I will be covering and I'll tell you when that happens OK and you'll you'll notice when it happens OK if you want to get ahead start reading chapter to chapter 1 is pretty basic Chapter 2 then starts getting more advanced some homework due to problems in Chapter 1 all the odd problems and also all of the asterisk problems and let me add that that to so all the problems that have an asterisk are built the answers to all the problems of an asterisk are available online so I'd like you to do
this as well OK and then in addition I will be posting a work sheet number 1 on the site it's not there yet but be posted notices will be posted after it's OK said I will be posting that that will form the basis for the discussion sections please work the worksheet as well OK so before I get started out before I go through very much more on tell you are what you should be paying attention to words and the 1st thing are these announcements and giving on what's discussed in lecture the discussions so they give you a lecture are your guide to what I think is important OK so right before the midterm you're going to want to know what do I need to know on the mid-term to get an a in this class and my answer is always the same which is what I talk about elections when I talk about a lecture is what I think is important have a limited amount of time for these lectures and I'll be doing to lectures per chapter of an hour and 20 minutes each and so on if I talk about it in lecture I'm telling you I think is important this is something you need to know for the mid-term OK and so what's discussed the lecture is reported this includes those slides and anything else that's posted to the Website on discussion worksheets and then the discussion in discussion as well if you're sitting on the left side of the classroom class students who listened to if you have an empty chair in your right said just to create more extra chairs because we have people arriving late service future replaced thank you I'm OK the next most important thing a sign reading light filter the sign reading through the filter through the lens of what I talk about in class if I talk about in class that's telling you it's important if I don't talk about it the less important and then finally the problems in the textbook as we support the good news is there's a few things that you don't have to worry about and the 1st Eleazar references on the slides I find it almost impossible to do stuff that without having some referral back to the literature and that's part of the nature of scholarship and it's totally impossible to get me to stop doing this and when we went even I wrote the textbook for example we had a list of references it's like 10 times longer than the 1 that's posted to the Web site and I we found it totally possible publisher told us to stop doing it to leave out those references and so and references are basically that currency that underpins and 1 I'm telling you but on the other hand this is an introductory class so don't get worried about those OK if you take a graduate class may have references on slides you want to look up those references but in an undergraduate level don't get worked up about the case said don't stress about those in addition don't stress about stuff that's covered in the textbook that we don't discuss in class specified United exodus before a final discussing class and it's in the textbooks don't worry about it a case of the text is written as sort of an advanced undergraduate early graduate level and there's material there that's frankly graduate level but I want you to get stressed out about it a case of I don't talk about and class that's my signal that I don't think it's so important for you to learn that the questions about what I'm telling you the thing I answered a question Commissioner David Marin could you look into the affidavit in OK so go be eventually will appear there but not yet thanks for asking the question was now so we will not be collecting the problem sets but plenty of other chances to learned about intelligent creatures from another question slides will be posted perhaps that's a good question all tried by unusually frantically getting ready the daylights out onto my that's certainly the Thursday lecture will be but maybe not the Tuesday of the library that's other questions OK more background of course instructors on Professor Weiss I've be teaching his class for about 12 years and I absolutely love chemical biology is what makes me want to work it's is my sole passion in life was that's a little bit of exaggeration but close and OK so what else would you like to know about me here's your chance for the next 5 minutes you can ask me anything you want personal not personal go ahead in the back I so my laboratories at the interface a chemistry biology and were trying to develop new ways of looking at individual molecules and under undying setting how membrane proteins work thanks for asking him a question over here it was a kind of a competitive guy I like driving fast I liked the horse racing and so yeah question over here chemical biology emphasize that this is a great question so the question was What is the difference between biochemistry Chemical Biology Chemical Biology emphasizes what's happening at the level of Adams and bonds and biochemistry emphasizes what's happening at a larger scale so in biochemistry and my colleague circuit tend to look at proteins sort large molecules without getting too worked up about hygiene volunteered Hajime bond there sometimes they get worked up about the things that most the time on the diagram signal transduction diagrams and things like that are just large blobs and in this class will be zooming in and looking at the actual Adams and bonds a the question I'm anything else personal this is your last chance as being personal that's not my pets my hands so go ahead now I wish I did I only get to go out once a year it's kind of the limitations who's not thanks for asking OK well I should also let you know I have 2 cats and unmarried and that's it for the personal information had been OK let's question go ahead of you have 0 kids for a two-seater cars without OK guys and that's it on the personal stuff enough about me and I'm very pleased that this quarter we have really the very best years in the chemistry department I've gone through an IFA hand-picked by
ITA is Miriam if the car is up and there is a great example is Miriam and I talked this class last year and I she knows everything there is to know about this topic and her research is a chemical biology and she's actually superb and if she tells you something about the class you could take that as good as coming from a local farm in addition our 2nd TA could Millheim isn't here today she's been tied up in India but should be back in the next week or so and she is also a great source of information she also a graduate student in my laboratory tests were really lucky to have him California's finest natural resource cheering for us a critical and Miriam OK so terms of office hours I will be having to office hours a week my Thursday office hours set by Wednesday office our however will float a case I will always have office hours Thursday at 11 today there was this other office tower the 2nd office our will float meaning that my schedule's costly changing it's all have to change the surround a case so every week I will announce when an officer will take place if for example my office hours don't think your schedule tell me at the beginning of the week when you like my office hour to be an altered my best to accommodate as many people as possible each with effect so 1st office our fixed 2nd office our floating I will always have office hours set up in a way that's at the interfaces between classes so you don't have to attend the whole office hours if you can attend as the 1st 15 minutes or so or 10 minutes and then fly after class that's perfectly OK short for 5 minutes get your question answered and then disappear I don't care I don't mind but always set them up so their time at the junction between classes that then you know it's less likely that you'll be able to tell me that you have a scheduling conflict with every 1 of my office hours I've heard that before and I usually ask those people to show me their schedule classes and I've never seen it actually that way especially since I had the 2nd office flooding so as to me plenty of time for you to meet me this quarter and in fact I really want to get to know you have I will get to know the names of 95 per cent of you in this room I will know something about what you're career aspirations are and I will know something about your creativity in terms of your ability to come up with novel ideas you're writing ability and a lot of other characteristics as well so at the end of this I will deal to write a very good letter of recommendation for you OK and this is not a proposed last topic but I would like you to shut off your cell plays cut and that also includes text messaging as well thank you I'm OK so anyway come out my office hours especially in the 1st couple of weeks introduce yourself tell me why it is you're taking this class what it is you hope to learn what it is that you're hoping to do what you graduated from UC Irvine and if there's anything I can do to help you in that course I will do it OK that's 1 of my jobs and furthermore even after you graduate from this class you can still keep in contact with the can still get letters of recommendation from me and you can still have my support in your career aspirations that's my promising commitment to you OK and on the TAS also have office hours each week here office hours will always be on different days and times in my office hours and their office hours are much more fixed that my office hours so any questions about anything I've ever said any of announcements so far OK I very textbook parody of mention this again it's available on on Amazon understand it sold out but you can get it again from Amazon supplemental text I'd like you to have available in organic chemistry supplemental text when I talk about peptides for example when I talk about in bonds I'm going to see that you've read the chapter on Emad bonds and peptides in this supplemental text even if wasn't covered 51 state a pale just ask you to go back and read that chapter of pay and say you need some sort of supplemental text available in organic chemistry .period as basically as reference it's nice because this will provide a kind of a lower key our treatment of a more complex topic server example if you wanna learn the sort of the ferry fundamentals of DNA of carbohydrate chemistry the best place to start is whatever textbook used to 51 C now I realize many a few soldier textbook right after the class was over there was a huge mistake but it's not too late to change things number 1 but I can give you are alone you a supplemental tax if necessary come to my office hours 1st by people a shot will get 1 of those and 2nd that the the library the Science Library has about 3 shelves there like this wide the field of organic chemistry texts the exact text does not matter a paid basically if you look at some organic chemistry but textbooks they're all more or less the same pay what really matters so as have 1 available to you that you can refer to as reference you need that for this class of Haiti's I'm going to assume that you know the material in there now along those lines spiked on a couple of e-mails from some of you are concerned that you had trouble in 51 C a troubled organic chemistry and now you're taking the sort of advanced organic chemistry class in your worried OK here's what I want to be there 1st don't panic pay I will do my best to get you up to speed on Aguero pushing and some other fundamental common fundamental principles in the next 2 weeks they later don't panic yet at the end that 2 weeks if 1 I'm doing on the board and your ability to keep up a discussion section and homework are just you know apples and oranges you know feels a part of the uniting on the same racetrack then you can start panicking but for now no panic a play and if you were really really weak in a soft organic chemistry I'd like you to open the chapters on carbon he'll chemistry whatever book it read the chat reread the chapters and Carbondale chemistry and get up to speed on those if you understand how Karniol chemist heels react called Alpha carbon is acidic and a few other things he'll be fine in this class turns out that's like 60 years 70 per cent of the organic chemistry that underlies biology involves carbon yields cases start their 1st AFC the advantage of the carbon deals come see me again and I'll get you don't give you the next topic which will probably be a means or something like
that appeared some Texas hopefully have allayed some of your fears .period don't panic yet but I get ready to panic in the next week or so and also to get ready to take your game up a notch OK so that you know even if had a bad time 51 see you can do pretty well miss classic you're ready to work pretty hard need lots of problems and come up with creative ideas center OK found discussion sections these are mandatory this especially important a few weak in organic chemistry discussion sections are going to be run in a problem-solving format and this is your chance to show that you could do era pushing with the best of them so a lot of the problem from this class involved mechanisms and set in discussion sections you'll have a chance to demonstrate your ability to do mechanisms you'll you'll get up to speed on doing these correctly etc. OK so again the 1st work she will be posted shortly the 1st discussion section will start this Wednesday and Marion will be teaching that 1 and then after that it will continue but could have your honor Monday if you were scheduled for Monday discussion section of don't panic what the material that will be covered on Wednesday will then be covered on the next Monday OK so we'll have them slightly staggered throughout the class OK and it turns out that actually works out fine because the midterms are on a Thursday at a Tuesday case there'll be 2 midterms in this class and on there are no makeup exams available and they they will consist of the full hour and 20 minutes but there's going to be an emphasis on pushing and constant problems will be things like short answer there'll be no multiple choice and there's going to be like short essay type problems will be problems we have to design experiments things like that but lots lots of Europe which said get ready for air oppression is on in addition the other way that I'm going to assign your grade is I'll be looking at 2 written reports that you're going to submit in the class the 1st of these is the Journal article report due unfortunately on Valentine's Day Happy Valentine's Day from your chemical biology friends on and in this 1 and this report you're basically going to be doing the equivalent of a book report but using an article from the primary literature to provide a report I've already posted to the Web site an example of this and in addition instead of a final exam this class will have a mandatory proposal that's due on the last day of class March 14 OK that's and mandatory proposal you cannot pass this class without turning in of the proposal but there's no final exam day and the proposal will consist of an original idea a chemical biology now I know this is daunting I thought this classy foreign notices really intimidating don't panic and I will have a series of exercises for you this quarter that will get you up to the point where you're ready to come up with creative novel ideas in the cutting edge of chemical biology so you will be ready for this you'll be ready to contribute and the good news is a chemical biology there's so much that we don't know but there's lots of room for smart people like yourself to come up with a really great new ideas can I see this every year every year I would take the very top proposals from art from this class and I could resentment in the National Institutes of Health and they would get funded had the best ideas I can put up for faculty ideas anywhere OK so I've seen that before and the other thing is I'm looking for a small idea and not looking for a you know the next Manhattan Project or something like that I'm just looking forward to a base said you know something that will work that will teach us something new about chemical biology and you're going to I'm quizzes I will have a series of quizzes in this class bomb that will number between 1 and 5 became more likely to be 1 to 2 there will definitely be a acquitted 1 sometime in that last week and the reason is our 2nd midterms in February and the classics going till March accessibility and easy quiz the quizzes in general are designed to be easy they're basically you recapitulates something that you just saw on the board of peso will run the easy there at the beginning of the class of the the class cannot be something along the lines of the Solis mechanism show me again how it works OK something like that just basically tells me whether or not you're paying attention and he's showing up for class and by the way I'm delighted to see all of you happy people up this morning but welcome but I know as the class wears on you guys get very uh the busy and I Of course lectures will be posted online there has to be some incentive here to get you rolled out of bed at 9 30 in the morning OK so and we will have some quizzes it will be too many and they will be hard to that I promise you in terms of per cent of your grade those quizzes only account for 5 per cent the same level of participation participation counts about lecture and discussion and on for that matter even office hours peso being and Marianne mn critical getting-to-know-you that's how we determine the the the quiz courts are the participation sport 0 and by the way I am I will post all these slides online a possible be all opposite the website on steel have copies of them not personnel but the because the shortly OK each major will count for 30 22 per cent of your total grade but the Journal article report will account for 16 per cent and the proposal which is in place of the final exam accounts for 30 per cent of your great pesos a pretty even distribution there's lots of opportunities to get for you to get feedback etc In questions so far yes in that was honor it is I haven't talked about that yet takes readers that agog at that in just a moment of Thanks for and I me Steve now question Carl OK Carl he had no problem Carl's question is whether a and assigned to some discussion section doesn't fit my schedule to another 1 No problem and you can even go to 1 1 week in a different actually the problem the and posted online will are it's posted on the syllabus exactly when the discussion sections will take place and let me
show you that "quotation mark so this is the course website pay on notice over here that there are instructions for the book report all changes very slightly after 2013 instructions for the proposal all changes very slightly there are 3 examples of proposals that are today and then the syllabus In the syllabus of 5 listed the discussion sections and where they need etc. feel free to go to any of these Hi I'm let me zoom through this this is online I'd like you to read this carefully I'm going to hold you to all the provisions that are in here a peso anything that's written in near it's equivalent to me saying I'm not sure exactly why this is because of the rain I In a lot of this recapitulates what I just said OK let's get to this on this question Over here and there will be C 1 moment OK on February 20 1st 2013 you will turn an abstract for your proposal OK so abstract is the short condensate of what your proposals going to consist of this tells me whether or not you are on track and I'm going to use this as a way to give you early feedback about your idea and tell you whether or not I think your idea fits the definition a chemical biology whether or not I think your idea here is a creative 1 or not so creative OK so this gives me a chance to give you feedback before you turn in your proposal the and on this abstract is worth 10 per cent of the points for the proposal assignment a case in other words 3 per cent of your course created will be determined by that abstracts of papers note that all assignments are due by 11 AM on the due date there is a league policy but I hope that doesn't apply to you questions of rights yeah never distracted by this information here about ads and drops on news that frequently have asked questions section 22 10 discussion sections yes discussing paper turn in the final assignment at all if you have not taken all three-quarters of 1051 2 semesters of organic chemistry you should drop the class OK you're going to get blown out of the water in case so you must drop the class now it's a prerequisite and that every year someone slips through don't take this class if you haven't taken the .period Organic Chemistry Series have I'm OK there's a whole thing on incomplete over here but no economic policy unfortunately we're going to talk about this later in the class I do not want to apply to you there that the major portion of greatest .period to be writing assignments and so academic integrity issues loom large unfortunately in this class every year I have to give someone of of F grade on assignment which and that's turning into like a C minus D plus kind of deal because they try to plagiarize assignment don't let that be a let's make this the year don't have this problem and along those lines if this is the year I don't have any plagiarism problems I will give an additional 3 per cent higher grades solve assigned the grades and then I'll go through and all pumped up 3 per cent of the course grades to the next higher grade OK so if everyone in the class avoids having any plagiarism or academic honesty issues said no cheating on exams no plagiarism no academic honesty I will bump up the grades by 3 % became means for 5 of you at each level are going to get a higher grade OK so that means like 4 people 3 or 4 people who were going to get a B-plus ,comma variety minus I'll take the top of the 3 or 4 top the minuses in movement today OK that's the deal will talk some more about this because it's a slippery slope and it's best that we don't have that this ,comma conversation later OK so anyway on that's information on the best-seller
syllabus ,comma holding due entirely to the US contents of that sold some expecting you to go home and read the Silvers carefully I don't have time to talk about every aspect of it now I'd like you go home go and read it carefully please current questions questions OK that you that OK let's get started so we are adhered heard the question what is chemical biology Hauser differ from biochemistry I gave me kind of a quick answer I want to delve into this topic a little bit further OK so here's the working definition of chemical biology that will be using this quarter and it's important that you understand that this is the definition is using chemistry to advance and understand molecular understanding of biology at the level of Adams and bonds so the way I know that we're talking at the level of of of molecular at the molecular level is if we're talking about Adams and bonds OK and that's what I'm looking for in terms of definition of chemical biology there is a on a 2nd corollary to this definition which is using techniques from biology to advance chemistry and some examples of this are for example using molecular biology techniques to develop ,comma tutorial libraries of chemicals which is something that will is 1 of the projects of my own laboratory does affect so there are 2 parts this using techniques from chemistry to study biology or using techniques from biology to solve problems a chemistry in both cases these involve looking at molecules at the level of Adams of bonds and that's where it's distinct from biochemistry biochemistry also uses techniques to chemistry but oftentimes there with looking at molecules search amorphous blobs that are represented as you know spheres or something like that in textbooks in this class will be down at the level of abounds in bonds and that's how you know we'll be talking about chemical biology cell leader in the class when I asked you to come up with an idea in chemical biology a proposal idea that you should be thinking at the level abounds in bonds and then unit tells you whether or not your idea would be acceptable OK so Chemical Biology advances both chemistry and biology and I want to give you a couple of historical examples of this and for my money the very 1st chemical biologist was Joseph Priestley does this guy over here he was a remarkable and character so the isolated oxygen and other gasses cases he was isolating these using electrolysis and other techniques and on he would isolate these and bell jars and then he'd use these chemicals to study biology so 1 of the experiments he did for example was subjecting poor mice my said he would travel from fields and to these different but chemicals that he was isolating any found the mouse for example can live in oxygen but could not live in many of the other gasses that he was isolated OK so that's really interesting example because using the very latest techniques from chemistry to understand better how respiration works how organisms taken oxygen and at the same time it's using a technique from biology as a way of solving a problem in chemistry and the technique of biology is does the mouse lives or dies does the organism can organisms survive under these conditions to tell me something about those chemicals right Joseph Priestley didn't have any spectroscopy available to him so he's using a technique from biology Avery qualitative technique to be sure but I'm the nonetheless to and to tell me something about what's happening at the chemical level cake now and suggested .period Joseph Priestley had radical ideas about colonists in America and a theological dissents that were going on in England at the time and I like to say that the very 1st chemical biologists had his house burned by an angry mob who who came rampaging through his village with pitchforks and I work out literally to get his head and we had a proud tradition ever since of iconoclastic thinkers and independent people who were guaranteed to rile up the masses and but of course is not getting burned at the stake houses marketing burned because of his chemical virtues but this was a carried on by a series of Sir Humphrey DAT who shown here at the Royal Society of Chemistry on conducting experiments on his colleagues he had minimum inhale bags made out of silk that include gasses and then he's looking at the violent but excretions that happened afterward and so on this is just a classic would cut from the period OK now the others so these are sort of hourly workers part perhaps the most historically the most important experiment chemical biology was stunned by the great Frederick Fuller in 1828 there's a picture of a notice of these guys are pretty young OK these guys you know we were doing this stuff in their twenties opinion not much older than you any of you in this classroom 5
years from now you could also be doing stuff that would change how we think about the universe yeah that's way science works as 1 of the great things about science OK so I don't think about this is being done only by old people it's not done in the East great ideas are often times done by young iconoclasts who have clever ideas and just wanna push the bounds OK so here's frigid polar on 28 he's ready experiment laboratory where he's running this this this silver signed experiment where he's trying to do what would be like that just the most pedestrian of exchanges of salts a case so when he's trying to do is synthesize ammonium signed 8 using silver chloride which he knows will precipitate out recall from Kam 1 that precipitates out in a white powder and he's doing this by simply mixing silver signed a together with ammonium chloride and he's expecting when he that the silver acquired will precipitate out and will be left with ammonium signing it turns out that's not what he got a that was not the product that occurred instead what happened was he got out this other products that crystallize out of reaction flask and when he said well this other product he knew immediately what it was like he smelled was urea and you really have been isolated from Europe from dogs and humans and so it was known that you really is is a known compounds and back down and then the primary way of idea of characterizing the chemicals was by the smell by the taste and you know some the most physical properties and because you really has a distinctive smell he can readily characterize now here's the significance of this discovery what Frederick Voller recognized was that this year was tentacle to the urea that obtained from dogs and from humans but the differences this did not come from a living organism In other words using just mineral sources you can miss seeing chemicals that are found in living organisms so there's not some sort of special property that animates the chemistry of living organisms that somehow makes it special instead it's going to be governed by the same rules that are found a chemistry that's outside living organisms OK and this is really important because at the time there is this notion that living organisms would have some sort of special spark that in some way would make them of a wife and make them make their chemistry unique and special and wonderful were showing us by this experiment is that in fact there was nothing unique and special about the chemistry inside living organisms OK so these are great examples of using chemistry to understand biology at the level of Adams and bonds in the case of urea and let's move on another principle that underlies chemical biology is evolution were going to be talking a lot about evolution in this class and so on the reason we're going to be doing as it is our 1st it simplifies knowledge and 2nd it's going to I'm guide experimental design and I'm appears to views of the great Charles Darwin we can talk about evolution without making reference to Charles Darwin you articulated in you know 150 years ago much as you know the principles behind evolution 1 of the 2 steps evolution the 1st step is to diversify to generate a diverse population of molecules of organisms of the other phenotypes relate and then the 2nd step is to select for the fittest from this diverse population all explain the word phenotype at moment I don't panic if you didn't work so simply 2 steps here select for generate diversity select for Fidesz the steps and then repeated again and again to evolve organisms that can solve some sort of problem in terms of chemical biology we think about generating diverse populations as ways of shuffling together shuffling around the fire with only Mercer Inc ,comma tutorial matter become material manners and after you that in a moment In of we often do experiments that involve some selection for fitness were going to make a large population of molecules mix them up and pick out the ones that are most of that can best fit the criteria were set of conditions this is a very powerful principle that allows us to make progress very quickly in chemical biology and say this is used as a technique by hundreds of laboratories in the field and so we use of evolution not just as some sort of theoretical underpinnings but we also uses as experimental framework and I encourage you when you think you about proposal ideas think about that evolution as a tool to to help you and speed up getting toward molecules that you stuff for you said this is used extensively in another way that use
extensively is used to organize knowledge when we talk about unsavory writers of which is the machine that translates them RNA into proteins and I'll show you what that looks like in a moment on I don't have to talk to you about some sort of special ribosome that's it found exclusively in humans but war dogs or something like that because it turns out that the same mechanism used by ribosomes in humans is also used by bacteria it's even the same mechanism used by aka bacteria a different stem on the tree of life entirely and so what this means that is that I don't have to teach you about the special chemistry of humans I could talk about the chemistry that underlies come all organisms on the planet because we all evolved from a common ancestor is that's all these mechanistic problems in chemical biology effect so this provides of this provides a powerful approach to evolve molecules which I alluded to in the previous slide but equally importantly this help helps us to organize knowledge and make it much simpler for us to talk about about universal chemical mechanisms that underlie all life on the planet OK so speaking of certain universal the principles that underlie all life on the planet the central dogma of model of a modern biology and is used is going to appear in multiple ways throughout the score in the 1st Way this is how we organize the textbook that you will be using this quarter case of a textbook has different chapters and it's organized according to the central dogma so the tension central dogma 5 describes all biosynthesis that takes place in cells in on the planet OK so everything that you're going to synthesized in yourselves is in some way encoded by the central dogma the central dogma tells us that the DNA found in nuclei you care out excels is the blueprint upon which all biosynthesis is based his DNA is transcribed into RNA and then translated into protein OK so this is the earliest diagram by the great Francis Crick who recognize the far-reaching implications of on this this dogma very early on and this is his earliest example of is articulated look just like that we now know for example that there is in fact this fashion line over here is in fact a real life there an enzyme reverse transcriptase days that work RNA into DNA but on this line over here we're on is used as a template to make new copies of itself this line never materialize we have not found in many years of looking the factory great Chemical Biology proposal to come up with doing that OK so here's
a different way of looking at the central dogma of modern biology so but at the very top DNA this biopolymer appear is going to encode messenger RNA and fact all on days of this the conversion of DNA until the complementary RNA takes place using an enzyme called RNA polymerase had this is nice because it's going to be polarizing on this makes sense I'm going to be referring to enzymes and today and in future classes enzymes are proteins that catalyze chemical transformations case of these lower the transition state energy for key reactions that take place in the cell and here's our 1st example of this the enzyme RNA polymerase that's responsible for transcription in addition there's an enzyme DNA polymerase that allows replication of DNA to make new copies of DNA but when the cell has to divide Hey here's the ribosome that I alluded to earlier on a previous life that is responsible for translation of RNA into proteins the central dogma continues as proteins and then put hacking catalyze reactions that lead to other Bialik emerged that are going to be very important in this class of for example were going to see a class of bio rigorous called terpenes better used in them used by plants and microorganisms for signaling polypeptides a class of molecules it's very important as natural products and for Inter barracks and other and pharmaceutical uses and then a legal sack arrives that like him and say that decorate the surfaces of yourselves and play key roles in protein folding and key roles in cell based signaling became so here's my plan for this quarter we're going to have to lectures about each of the Bialik emerged that's depicted here a place in next week I'll give it all talk to lectures about unfair pushing this week 3 have to lectures about DNA week flora 2 lectures about on a week 5 on 2 lectures about proteins week 6 rides with 7 . he tied speakers terpenes so actually Ontario had for lectures total about proteins I can't resist them approaching died and so on yes lot a total of 4 lectures about proteins that everything else want to lectures about and will be covering a chapter a week in the class size so necessarily some of the material the textbook will be left aside and the runs still with me so far OK so I told you that everything that synthesizes the cell is synthesized in a deterministic way starting with the DNA up here and it turns out that's not strictly strictly true and so I want to explore a little bit more about what the subtleties of this concept so 1st of all we need to define what is the unit
of simple best so proteins and so far DNA sorry DNA is right out in units called genes OK where each gene is going to coach a single protein genes have 2 essential parts an on off switch and expressed sequence the on off switch gears on where transcription factors behind these are proteins that can encourage RNA polymerase to blind to the start of this gene and encourage it to start transcription case similarly the other there's promoters there's also other ways of shutting off the synthesis as well it gets complicated but this transcribed region then becomes the messenger RNA which is then translated by the ribosome into the protein down here OK so here's an example for example of a transcription factor binding to DNA and notice that the DNA has a structure that nicely accommodate the structure of this protein I'm going to be talking a lot more about proteins later but I want to tell you about a convention that going to be using Taser proteins hopefully as you know are composed of amino acids that are strung together by a common bonds if what I told you Tolley doesn't make sense we'd go back and read the reference supplemental organic chemistry text became so when we look at these amino acid on and we just look at the economic bonds and the carbon that's all to that hammered bond and we can trace out the back that back using these ribbon structures so these words structures do not look at the side chain of amino acids rather they simply trace out the sort of the scaffolding backbone of the protein price and so that's what these ribbon diagrams will look like and then here's the structure of DNA down here notice that this Alfie he'll call ravenous curlicue ribbon fits neatly into the DNA Major Group will talk much more about that later OK let's take a look at the world's smallest gene this is the Guiness Book of World Records for a small stream but in this case this gene encodes for position and C 7 0 are the gene will in the protein all code for it's called Microsoft migrants in is a translation inhibitor it's a protein it's Walter peptide short short piece of protein called a peptide that's used by microorganisms to kill off their neighbors cases microorganisms that growing your skin that grow in the the you know far recesses of this of the Walls Unit grow all around you are constantly fighting chemical warfare with each other Hey their goes article the neighbors and then give themselves more resources that allow them to come to grow better appear to grow faster and to be more populist protect and my person is a good example of 1 of those aren't tied Bionics word compounds that killed other organisms OK and that this is actually a very complicated .period toxins that on the 1 hand there's this peptide over here that allows democracy said to be transported into the competing bacteria cases of bacterial look at this complicated thing they understand that the peptide regional think that that peptide looks yummy and if I eat that I'll get a new acids as they come as a source of building blocks for my own proteins that that's kind of like the beach OK so very competitor picks up the bait transports and my Creson into my presidency 7 it into itself and in which case the enzymes in the competitor then break apart but this this be this pact at this peptide and then unveil the translation inhibitor down here that shuts down translation by the writers on this is very bad news for the competitor right if the competitor organism to microorganisms cannot translate them RNA into proteins it cannot live it cannot divide it will die very quickly fade and so on In a sense of what we're saying is that the
smallest gene is rather complex it's toxic fragment is highlighted over here I and the rest of it also plays a key role as well OK so this To make something as complicated as this requires a large number of genes that are lined up over here where each 1 of these heroes represents a sequence of DNA OK we'll talk more about the direction only if they arose from world leader in Week 3 for now don't get too worked up about it notice that that it takes several genes to compose this toxin OK so some of these genes are doing things like adding on this non peptide like toxic fragment OK so some of these genes up here Our encoding various and enzymes OK so that's that's my person this and CCB and CCD unceasingly enzymes so these enzymes are adding on stuff and modifying the peptide that was otherwise encoded by and CCC In the center over here parasite and CCK there was a coded up here now at the end of this those as the world's smallest have you know that was you know smallest Jean delivering a tiny little peptide the resultant peptide is still fiendishly complex case this thing includes a large number of different stereo sound indicated by the dashes and the wedges on and furthermore this isn't the half of it right this is this it's very simple example the proteins will be talking about the proteins have been showing you today for example a transcription factor consists of hundreds of subunits hundreds of amino acids each 1 lightly with the stereo sound and so on that the the chemical biology considerations become enormous we start looking at this in greater detail and so we've looked at a gene let's talk next about the collection of genes all of the genes together that are found in organism are referred to you as a Gino here's 1 representation of the Member of Ojeda of the bacteria and model system bacteria called the call life will be talking a lot about the call I have another slide about a moment but this is used extensively in chemical biology laboratories including mine and its GM looks like this we're in this representation is shown as a circle and each 1 of these colored but FAA's tells us something about the size of the gene whether or not it's GC ,comma whether it's GC richness says etc OK so reading out the deep information here not so important but suffice it to say that the human genome has around 24 thousand or so genes and and when you compare that against almost any other machine that we have around us this number sounds ridiculously small 1 of the challenges however is even know we have this complete parts less for simple organisms like life it's not clear what each 1 of these parts is doing and so a goal of functional genomics and a goal for that matter of chemical biology is to try to make better sense of what of these parts less faith and let me show
you what I mean on the next flight became let's imagine that you had become a transmission from the car OK and so on imagine that you had a parts list of all the different years from transmission and I can tell you from some experience that just staring at those different years even you know steering as far as you possibly can and using your best you know sort of logical reasoning and you never really really hard time trying to put together each 1 of those little gears effective and hear how smart you are ahead handsomely oddball and so on we have that same problem when we look at you know what we look at GE announced it's not clear what each 1 of these parts are doing and 1 of the roles of chemical biology is to help us Kennedy chinos and teach us about what each 1 of those parts is doing in terms of the larger machine we'll talk some more about that there will be a topical and functional genomics OK so chemical biology helps us fill in the dynamics of the process and how these pieces fit together OK so 1 way that fills and dynamics dynamics means change over time is unimportant area chemical biology and develops new tools that allow us to see molecules at the single-molecule level and understand how the change over time and economically in a converted to different speeds and other things like that and Miriam is 1 of the world's experts said that she can tell you more about that now another big challenge that we have is
that I often times we have big differences in gene announced that the to the same species here for example are 3 different strains of the of the mall of bacteria the coli case of years 3 different strains and only 14 per cent of proteins are shared between these 3 on notice that they look identical and they're all the same species because they can and they can make taken by exchange DNA with each other and which in terms of bacteria it turns out is not necessarily the same as being seen species but in any case these are the names all the collide yet they have vast differences in what DNA they've picked up from their environment and from other microorganisms so simply knowing a parts list is not going to be enough rest explain what similar and different between these organisms OK and for that matter and we start looking at different we start looking at different organisms from the same population we see a similar sort of diversity despite having very very very similar gene OK so
I've been talking to you both about humans and also bacteria and I need to I'm hopefully just very briefly review for you that clear differences in those organisms are vast prepared on hopefully not telling you anything you don't already know and bacteria are classified as pro periods humans and other multicellular organisms or organisms even at a single cell that have multiple apartments in them are classified as you carry out but I'd like you to Our I'll tell you that in a moment on the big difference here is that the probe periods don't have any compartments for the most part the DNA is kind of organizing to nuclear lowered but for the most part there no compartments inside the cell of a pro precarious whereas when we look at you periods under a microscope and we find something totally different what we find is a bunch of organelles which of these little compartments from here and these organelles have different functions for the cell rather than being just the big bad that has all of the functions being carried out kind of randomly within that OK now
getting back to this idea of GE announced a nearly identical gene islands can lead to very different people so even know Our genomes are 99 . 9 per cent identical we see vast differences so this is a challenging concept but what's happening here is vast differences in transcription under a law these different phenotypes that observed where phenotype is the physical outcome of the Jedi OK so all of us have roughly the same Jean arms yet the phenotypes that come out on differ at the cellular level by on different transcription levels that program ourselves into having different functions so even know each 1 of these cells has the same gene on the cells and of having different functions by having different transcription levels of different sections of the G-8 different different genes with Imojean and furthermore at the organizational level this place out there and in other ways as well also at the trip level of transcription OK so here's 6 different human cells and you could see the vast differences in their should morphologies the shapes and can of etc. and for that matter I don't think I have to work hard to convince you that these have very different functions inside the organism in this case humans OK so I showed you briefly Epoca excelled over
here I'd like you to memorize all the structures and everything that's labeled here and labeled in the book by the the textbook location memorize the structures and
along the same lines I'd like you to memorize all the parts that are labeled in the textbook for you cannot itself OK so you should know basically that the simple anatomy of itself had the basic functions if it's in the book yeah I'm looking OK and so we've looked at DNA DNA gives us genes which gives us GE announced next section down on the central drama is on a cell from on the day that complete collection of RNA transcripts in a cell tissue organism is called the transcript on OK so here's the DNA genome of organisms here's a bunch of RNA transcripts and on the number of copies of each 1 of these transfers is controlled by transcription factors that I showed you earlier said that was alpha-helix fitting into the DNA if that if that transcription factors very effective not or any plan raised then you'll get more copies of the Emerine transcript .period being produced paper so these more copies of the transcript being produced can give rise to very different phenotypes of organisms so ultimately a lot of the phenotypes that observed are being driven by differences in transcription in addition to differences in the including DNA the resourcefully carry things little bizarre annexed it turns out that the RNA that's being covered by the deal by DNA it is further diversified by a process called RNA splicing itself on splicing takes on a that's encoded by the DNA and then sort she shuffles around very suddenly became the results are a bunch of different commodities including potentially different proteins down here take and the results sometimes traumatically differences differences in the resultant proteins so these proteins the consequences of this can be some proteins that have very different functions from the starting the starting and Morena nite you can end up with 2 different proteins splice variants of of each other there encoded by the same DNA that have different results inside the cell and different phenotypes for now there's going to be
further diversity but just to organize things so we've seen at the DNA level the collection of all genes discovered you know we've seen it on a level the collection of all RNA transcript is called the transcript and then at the level of proteins the collection of all proteins called the Prodi Pegasus there's a sort of a neat but organization to all of us OK now what I'm showing you ever to showed you this is the representation of the gene free call like this is a way of rate representing the transcription of using a technique called RNA might ratings will talk about this morning we for and you could do a similar thing make a big collection of all the different proteins found in the cellar organism at issue and a rabies on microscopic slides as well so all these techniques are ones that will talk about a leader in the class OK so we talked about how you can start with an already transcript history yes it the life of the church in on OK so what you actually OK so actually questionnaires on what actually gets translated on the messenger RNA and In this way into the yes what actually gets translated into proteins from the messenger and because this request and now they have a right to know and to train yes the only other thing that Texans I'm going into the on Army OK so your questions were settled that case so that I could further we get 2 weeks for which is OK good question will the organization of questions OK so we've seen how splicing can start with transcripts and then add additional diversity it turns out that proteins are also subject to diversification as well so after the proteins are synthesized by the ribosome during translation these are subject to further diversity in a couple of different ways became the 1st way is for the proteins to be modified chemically on the surface and so on 1 example of this is an elongated factor too so this is post-translational modified to produce this functionality up here called victimized OK so the protein is enzymatic late converted it from having to submit all functionality of peer into having it did my father functionality this is absolutely required for a translation by this organism organism being human OK so long nation factor too that's been post-translational modified is required and for translations to take place however they did .period toxin has a way of cleaning off shares I did my head when that happens that prevents protein translation from taking place they diphtheria toxin fascinating it's effective way of killing cells on what's important here or there is this notion that even after the proteins are synthesized their further diversified by chemical reactions that take place on the surface because this takes place after translation these are referred to as post-translational modifications guide post meaning after translation modifications translational modifications and this is really important this means that we can start with say 24 thousand or so genes in the genome get you know say 50 thousand or 60 thousand different splice variants gets a 60 thousand different proteins and then further diversified 260 thousand different proteins into to enter for even more thousand different proteins so in the end although RG loans look relatively on complex at the level of 24 thousand or so different parts of the true number of this vastly understates the true number of parts which is much much larger due to reactions like this 1 can furthermore these proteins go off and catalyze other functions within the cell leading to further diversity everyone still within the post-translational modification let me show you what I mean by that I'd refer to this as post-translational processing so this is the process by which proteins and catalyze as enzymes from the production of other molecules elitist Sack writes glycans polypeptides centipedes OK so far out once the enzyme is made it's just the start after that all kinds of other things take place OK and this is proteins can be barely altered by enzymes that's the modified proteins they showed you on a previous life in addition there spontaneous processes that alter the probe on surfaces of proteins OK so for example oxidation of proteins is it's sort of an unavoidable consequence of having metabolism that's dependent upon oxidation right and producing oxidation products so there some strong oxidants that are produced by yourself and those oxidants will come along and modified the surface is approaching its spontaneously decay using Thurman economically accessible reactions and so this is these are examples of post-translational modifications in addition proteins themselves will catalyze reactions that was synthesized from these small tools down here tricked again are part of the central dogma thereby only that's 1 thing I have to tell you is that while I told you that the central dogma in determinists quake determines everything has been set aside by the cell while it determines everything synthesized by itself it's not truly deterministic OK and there's an element of randomness to all of this OK and that's what I want to show on the next slide this is works see we're going to have randomness in the sense that the central dogma will dictate the identity of enzymes and then these enzymes are going to go off at catalyze reactions that will not be determined by the unit that will will be at some level a little bit randomized al-Qaida so 1 good example of this is the process of the pending a legal Sack writes the the surfaces of protein case so far appears meant to represent a protein and each 1 the shapes is meant to represent a different carbohydrate go like him and that's being that's going to be but attached to the surface of the protein OK now the on the way this works is that each 1 of the enzymes that's going to do this attachment is encoded by some gene appear encoded by the DNA translated .period transcribed into messenger RNA which in turn makes the protein enzyme that's going to catalyze the bond formation that quite and onto the legal upright and what's less clear that on is no small variations in the resulting quite hands down here so for example the enzyme to makes bond if there's enough and signed to around maybe makes another bond and enzyme 11 makes this bond but maybe if there's enough enzyme 11 around maybe it makes another bond over here so there's diversity in the resultant structures that are found said that buyers synthesized by the enzymes OK furthermore you know I'm winding up the enzymes in this on the order of the genes in the genome is unrelated to the final product that results in this like him and on the surface of the the protein which eventually appears on the surface of a cell so there is considerable heterogeneity in these post-translational processes both in terms of modifications in the sense that some of these modifications are are occurring spontaneously just through thermodynamic Lee accessible reactions and furthermore when they when these post-translational prophecies are catalyzed by enzymes there is considerable still chasm randomness in terms of what the resultant structures will be OK so this is 1 of these entire mind-blowing concepts that we have to get comfortable with had every continent deterministic way knowing every single molecule must sell to a precise level everyone controls the concept don't look so manipulated downcast at the end of this class of legal least have a framework to understand things OK so and so I want to switch
gears now and talk about some of the principles different types of techniques that you need to know about them that were going to make our lives so much easier in thin and understanding of the experiments behind chemical Biology Caso earlier I told you that an important principle and chemical biology on according technique used extensively chemical biology is too make a large diversity a large diversity of molecules and then sift through this diversity defined a few molecules that do something special that is the technique of molecular evolution it's used extensively in chemical biology so there's going to be 1 equation in today's lecture that 90 children know and this is the equation that determines the diversity of the collection of molecules that diversity the number of only cameras that results is the number of subunits raised to the power of the length of the illegal OK and we try to show you dressed in OK return on some whites here
and so on let's start with the
United but they could be collection of DNA and DNA consists of 4 basins and ACG into again we'll talk some more about the chemical structure in a moment and let's try to imagine than that of a point to make a collection of all possible but catches OK OK so a number of possible DNA well that's it pensioners OK OK so the number of possible tend to burgers is going to be equal to need the number of subunits raced to the length of the only get the up by only OK 0 this is the number of subunits is for that's the number bases the and raised to the power of 5 that's because were making pensioners OK if we wanted to make a case of this is example of fibers if you want do 10 murders again we have 4 the 10 power this is a very simple equation very very useful it can tell you very rapidly whether or not the experiment you propose is reasonable rate if you propose something is going to fill this room with DNA probably not so reasonable right that's not practical but I if you propose something that you could fit in say a windmill test is totally reasonable or 1 or 2 of to that would work OK any questions about this formula ready to play look good but said 1 of the great failings of teaching class like this 1 is that the example problems at all due for you were reapplied equation or whatever inevitably a lot easier than the ones that appear on the and I apologize about that this kind of this part of pedagogy I guess OK now it
turns out that chemical biologists apply this to 2 DNA but they also
applied to much more complicated molecules and so for
example we can do it ,comma notorious the of a series of bomb molecules that look like this case so we can do we can set up a modular architecture to allow comment for all synthesis that found innocent in a way similar to composing by Alija birds will result in molecules that have modules that have been tethered together OK so for example this is this is a this is a framework called the pet toys OK and so instead of a peptide where the peptide would have a slight change coming out on the Gulf carbon over here instead this has sigh genes coming out on the nitrogen you could very readily make a large ,comma tore a library of of these pet and make a great diversity of numbers structures using exactly the same formula they should on the previous slide to calculate the resultant diversity occasionally show you how that would work if you have 20 subunits 20 different possible building blocks and you're going to make 3 murders then you would have 20 to the 3 three-pack power of 3 20 reached the 3rd power would be the resultant diversity of that that library where a library is a collection of diverse molecules had so this idea of ,comma Tawil diversity applies both at the level of shuffling around by Willie tumors and is applied in biology but equally importantly its use as a principle that analyze chemical synthesis in chemical biology as well including the chemical synthesis that you learned about back 51 C OK and we can get a much more complicated and make libraries have been so that is opinions which are shown here and this is an important class of small molecules on this very commonly used in many different drugs OK when we stop
here when we come back next time he'll be talking about diversity in biology
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Oberflächenchemie
Chemische Bindung
Kohlenhydrate
RNS
Genom
Molekül
Enzym
Krankengeschichte
Sonnenschutzmittel
Zelle
Reaktionsführung
Oxidschicht
Base
Zelle
Elongation
RNS-Synthese
Gen
Radioaktiver Stoff
Intron
RNS
Assembly
Messenger-RNS
Proteom
Tripeptide
Posttranslationale Änderung
Chemische Bindung
Periodate
RNS-Synthese
Diphtherietoxin
Enzym
Chemischer Prozess
Sonnenschutzmittel
Posttranslationale Änderung
Transkriptionsfaktor
RNS-Spleißen
Werkzeugstahl
Chemische Struktur
Sammler <Technik>
Elektronentransfer
Funktionelle Gruppe
Gen
Reaktionsführung
Membranproteine
Translationsfaktor
Biologisches Lebensmittel
Bindungstheorie <Chemie>
Wasserstand
Polymorphismus
Molekülbibliothek
DNS-Doppelhelix
Komplexbildungsreaktion
Quellgebiet
Setzen <Verfahrenstechnik>
Translationsfaktor
Gezeiten
Thylakoid
Toxin
Erdrutsch
Azokupplung
Toxin
Genom
Chemisches Element
Chemischer Prozess
Emerin
Chemische Biologie
Molekulare Evolution
DNS-Doppelhelix
Potenz <Homöopathie>
Sammler <Technik>
Setzen <Verfahrenstechnik>
Untereinheit
Molekül
Chemische Forschung
Lactitol
Computeranimation
Untereinheit
Chemische Struktur
Oktanzahl
Chemische Formel
Potenz <Homöopathie>
DNS-Doppelhelix
Sammler <Technik>
Chemiefaser
Untereinheit
Einzugsgebiet
Vorlesung/Konferenz
Chemische Forschung
Chemiker
Chemische Biologie
Tumor
Biosynthese
Pentapeptide
Kohlenstofffaser
Untereinheit
Chemische Forschung
Stickstoff
Computeranimation
Rauschgift
Chemische Struktur
Sammler <Technik>
Vorlesung/Konferenz
f-Element
Molekül
Lactitol
Biosynthese
Präparative Chemie
Wasserstand
Molekülbibliothek
Modul <Membranverfahren>
DNS-Doppelhelix
Potenz <Homöopathie>
Bucht
Erdrutsch
Gen
Untereinheit
Chemische Formel
Besprechung/Interview

Metadaten

Formale Metadaten

Titel Lecture 01. Introduction/What is Chemical Biology?
Alternativer Titel Lec 01. Introduction to Chemical Biology -- Introduction/What is Chemical Biology?
Serientitel Chemistry 128: Introduction to Chemical Biology
Teil 01
Anzahl der Teile 18
Autor Weiss, Gregory Alan
Lizenz CC-Namensnennung - Weitergabe unter gleichen Bedingungen 3.0 Unported:
Sie dürfen das Werk bzw. den Inhalt zu jedem legalen und nicht-kommerziellen Zweck nutzen, verändern und in unveränderter oder veränderter Form vervielfältigen, verbreiten und öffentlich zugänglich machen, sofern Sie den Namen des Autors/Rechteinhabers in der von ihm festgelegten Weise nennen und das Werk bzw. diesen Inhalt auch in veränderter Form nur unter den Bedingungen dieser Lizenz weitergeben.
DOI 10.5446/18860
Herausgeber University of California Irvine (UCI)
Erscheinungsjahr 2013
Sprache Englisch

Inhaltliche Metadaten

Fachgebiet Chemie
Abstract UCI Chem 128 Introduction to Chemical Biology (Winter 2013) Instructor: Gregory Weiss, Ph.D. Description: Introduction to the basic principles of chemical biology: structures and reactivity; chemical mechanisms of enzyme catalysis; chemistry of signaling, biosynthesis, and metabolic pathways. Index of Topics: 0:30:30 What is Chemical Biology? 0:42:01 The Central Dogma of Modern Biology 0:46:54 What is in a Gene? 0:53:31 What is a Genome? 1:00:33 Inside a Human Cell 1:09:58 Combinatorial Assembly Generates Diversity

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