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Lecture 02. Common Tools in Chemical Biology.

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OK welcome back the a quick Sanchez everything OK great thank you and welcome back today were going to be finishing up the topic that we were talking about last time last time we were talking about ,comma tutorial approaches in chemistry and then we'll talk a little bit about more about our common editorial approaches in biology and I'll show you a couple of examples of this OK but not sufficient OK so OK
so again we're here we just completed our survey of biomolecules I'm going to complete the topic of making common combinations of biomolecules and then I will talk about tools for chemical biology and this is really important because these are the tools that you're going to be using when you write your proposals so I'm glad you're all here today because of you actually need to hear this to be allowed to write a good chemical biology proposal which recall last time I told you I was going to substitute for the final exam this class there is no final exam in this class will not have a final instead on the very last day of class you will hear me a 10 page or so proposal written proposal with figures and I will be original idea something that no 1 on the planet has thought before you will be the 1st and it can be really fun because it's really great to come up with creative ideas and that's really the ultimate goal of science and science is really a creative enterprise articles are to invent new concepts to tell people New Visions of the universe and to do this we have to to understand somehow event these new of experiments to do OK somebody talking to you today about the tools in your toolkit that you're going to be using to do this assignment
I know Kerry talked about these announcements and skipping some stuff so I office hours I had office hours yesterday that got derailed by a student emergency and I know a least 1 you send me an e-mail about that I apologize and I will have office hours today and In addition of I send an e-mail back to that students so I apologize if he came by yesterday there is a student health emergency that absolutely needed my attention so I had to close my door to deal with that OK so apologies there and other office hours tomorrow so Miriam will have a office hour on Friday and hoping critical will be back next week and electricity to Argillite of office hours next Tuesday because so any questions about any of announcements things like that things that we talked about last time questions about the cost structure so I got e-mail from someone and I apologize for not replying to the e-mail was when he went to post online the on the slides that I'm flipping through and the answer is I'm going to try to get to that today and then my plan is to basically posts all of my slides from Creek from the previous year and said I wouldn't we still have a guideline for what the slides will look like chances are all heavily modify these slightly modified his depending on how much time I have before each lecture I mean literally 5 minutes before lecturers making changes to the slides Summers a possible the stop me from doing that I just love this still much fun so because that all the posting of that kind of a guideline for what the slides will look like in advance and then I'll come back with something that's more definitive a so the ended stays lecture than office all the weak ones lies in a definitive way but I'm also going to post last year's week-to-week three-week for etc. OK sounded had a questions about OK great I'm OK so when the
review what we talked about last time if there no questions about any announcements things like that really goes straight into the material look again and so what we talked about last time was the definition of chemical biology Chemical Biology uses techniques and chemistry offer new techniques from chemistry often techniques that had been invented specifically answer problems biology but not always and then these techniques from chemistry argues to address understanding biological systems at the level of Adams and bonds that's the goal of chemical biology to really understand how organisms are living probably do the things they do at the level of Adams bonds OK so I'm really fascinated to know I'm about that hydroxide functional groups that she donates a key hydrogen bond or provides a key um uh Bronstad acid to and some mechanism in an enzyme active site that's the part that makes me right to work this sort of the details of this I basically want to use the pushing that you learned in soft organic chemistry to explain biology and that's the goal of this class and that's a definition of chemical biology so on last time we learned about 2 key principles that organize biology the 1st of these is a central dogma which provides the roadmap for all biosynthesis taking place inside the cell Everything that this cell has to synthesize will flow through the central dogma This is the flow of information for biosynthesis by the cell so everything that yourselves will synthesize is going to be encoded in some way by the DNA inside yourself 0 and can I ask you an empty seat next to you to move over to the right just to open up some set some seats on the edges of some people I know are coming in from other classes so other classes there anything about about what our classes started so if you have an empty seat underwriting dispute over and leave seats on the heads that would be really appreciated behind OK thank you OK so the 2nd key on principle that we discussed was evolution evolution provides a principle that helps us organize vast amounts of knowledge and makes and really in and simplifies biology enormous later on and it's actually a principle that all of you are going to be applying when you design your chemical biology experiments because I will tell you what events that I will not accept any proposals that appalled experiments on humans OK so experimenting on humans has its own special topics that I can actually teach a whole quarter on came requires ethical considerations it requires tremendous design considerations it's nontrivial to sample for example a diverse population of humans and ensure that you're getting diversity so all of those considerations are beyond the realm of this class so instead what I'm going to ask you to do is experiments on a nonhuman organisms you might for example choose cells from humans or you might choose model organisms and by choosing those model organisms you're applying a key principle from evolution which is that that model organism descended from some common ancestor that we share and in doing so I acquired the same mechanisms that govern its chemistry and its chemical biology and so that means that we learn something about this model organism we can then apply that knowledge to understanding how humans work no naturally there's limits to this great if you're model organisms is a salamander and you're interested in understanding how the salamander regenerates its arms when you cut them off which incidentally would be an absolutely fascinating topic for a proposal right but there's a limit to how much analogy to do back to humans right we humans don't have that same mechanism obviously and it would be absolutely fascinating for me to learn from you how it is that you plan to apply the biochemistry major learning about stem cell growth too develops a limb regeneration in humans I would love to learn that a appeared on a so evolution is important to us because it provided it tells us that fundamental processes are more or less the same for every organism on the planet and I'll be show you a few examples in the next few weeks that illustrate this universality of chemical mechanisms In addition we also saw that evolution is is really a tool by which we can evolve molecules to do powerful stuff for us inside the laboratory and I wanna pick that topic up for us today focus on start there and any questions about anything that we saw on Tuesday OK I also got some really fascinating e-mails of front of some virologists an audience to point out there's actually a decline the corner virus protein that is known to start them on a template and then replicate or name that's actually fascinating I wasn't aware of that so there are exceptions to what teaching Your Honor trying to teach you sorta most general thing and yes the will there will be exceptions don't hesitate to point them out to me I'm fascinated by this exceptions to OK so let's pick up where OK before we do 1 last thought about this proposal Simon
but to do the proposal successfully which you have to do is you have to come up with a novel idea OK I will not accept any proposals that don't have something new in the case and all actually asked the TAC do Google searches and and literature searches of Pub that and other sources to verify that would you're proposing to do has not been done before thanks to you whether come up with the creative new idea sounds daunting but let me I'm provides some guidelines on how to do this so the 1st thing that you need but they are a series of experimental tools and their knowledge of the problem peso experimental tools I'm going to provide you today I'm going to give you a toolkit by which you can go out and start to address problems a chemical biology the 2nd portion knowledge of the problems you need to know that actually you know there's a key step in limb regeneration that's not so well understood that 2nd step comes from reading the literature pay in the 1st assignment in this class the juror or journal article book for the Journal article report is designed to help you addressed this 2nd day knowledge of problems OK so in doing the assignments that are required for the class these 2 things are going to come together a paid today we're going to address number 1 and then item number 2 you're going to get by Valentine's Day February 14th you'll have a journal article report and then in doing this assignment you'll be looking at the literature you'll start identified problems in the field that interest you because he'll choose a journal article that's relevant your interests I don't what for solace 1 of the dermatologist because maybe you'll find a chemical biology report that I uses skin cells and looks at saved melanoma development in skin cells and looks out at the level of Adams of bonds but I would love to hear more about that and then by doing this assignment you'll start to know 1 of the big unknowns in our skin cell tumor development 1 of the things that people are fascinated by their mother and designing experiments to address and you'll have the tools from this lecture that will allow you to address those problems have somebody OK and so on how to find the problem the 1st thing I need to ask you to do is start reading either science or nature of peso and I assume many of you science majors if you're not a science major reasons OK you're a fascinating case I'd like to talk to you later so come to my office hours introduced solids everyone else I said you're going to get to get a degree in science I'd like you to read the science nature pretty much for the rest your life pick 1 you don't have to read about and furthermore you don't have to readable I carefully just skimmed through them by doing that you will be informed citizens OK you will know more about science than 99 . 9 9 per cent of the people on this planet and furthermore you'll learn something about what's really cutting edge they only have to spend 10 or 15 minutes flipping through science and nature just looking at the headlines of seeing will be discovered the class of quasars out in unison our galaxy just doing that is enough to the help you will certainly have much better be incorrect cocktail parties let's say because and to the that's enough showcases his party eradication effect so and start reading science nature simply flip through them that helps you are identified problems the 2nd ways to look at pub or MetLife which are the same things and I'll be talking some more about pub Madden in a in a future election a so hopefully your you already know what pub that is hopefully you already know how to apply it all be showing you had applied to chemical biology proper problems at a future lecture but these are the 2 ways have to sift through literature defined stuff that's interesting and that grabs your attention because in the end you want your proposal to be about something that really interest you pay your spend a lot of time on this occasion many many hours and if it's not something that totally interest you know that's not somehow related to the bigger picture of your career aspirations it's not could be as much fun and in the end if it's fun you'll do a better job of all get a better proposal backed out of it and that's the part that interest me OK now I was reading I cheered the admissions committee in Department of Chemistry at UC Irvine and I was reading the application essays from all the wonderful applicants who applied to use your mind this year and I came across this wonderful "quotation mark appear at the more you know the more questions you can ask and said so those questions that you could ask those are the questions that you will be in the dressing with your proposals so our goal is to get your knowledge up to the point we can start asking those questions defense and I know this is all very this seems 3 abstract but it's not news obstructed a moment had some good questions so far are dumping too daunted by the assignment and it will all come together but when you're ready OK last
announcements next week's planned next week we're going to be starting on chapter to please him chapter to an advanced take a look through Chapter 2 even before I get to it Chapter Two is a review of their oppression Chapter One was a review of the biology you need to go and next week will be talking about Europe pushing and mechanistic organic chemistry that you need to know To I do Chemical Biology a peso next week wouldn't have to lectures on mechanistic era pushing now here's the deal albeit of town on Tuesday but I've prerecorded Tuesday's lecture and say trying a little experiment this year and I understand that the the video from Tuesday's lecture the last Tuesday's lecture is already available and it's going to be up shortly posted online OK so I will send you the link to last year Tuesday's lecture and at the same time I'll send you the link to the next Tuesday's lecture pay and so that next Tuesday's lecture than you could watch in your pajamas in the comfort of your your dorm room OK and so on we're going to try that for for Tuesday's lecture I think that's actually I think that will work on but I'll know very quickly if it doesn't work said and then Thursday I'll be back said Tuesday albeit Cal State only giving a seminar Thursday they'll all be back 7 but no arrests so that the next week's planned we're going to be reviewing important stuff from organic chemistry is mainly focuses on structural reactivity of Kerviel's if your weekend 51 C please read read this chapter on carbon reactivity structure things like that there might be 2 or 3 chapters for you to read on mechanisms involving Kerviel's especially the algal reaction 90 per cent of carbon-carbon bonds in chemical biology or made using an algal reaction you need to know what an Alltel reaction it's OK if this word Al balls totally unfamiliar to you go there and on the need to spend a lot of the time this week and reading about it getting familiar with the again of would assume that you know about a noble reaction when we get to it from now on the other hand in your review of US off organic chemistry don't get worked up about reactions for the said is a Carbondale containing compounds anything that you learned in and out of 51 see about how to make a carbon using PCC and is more or less worthless for this class of hedge against PCC is not found themselves it's doubly toxic and so on I think it is as your skimming through because a reviewing if necessary don't get too worked up about memorizing a bunch of being reactions and stuff like that of her instead focuses on mechanisms to focus on the reactivity understand how carbon work that sort of thing that's what you really need to know going into the next few weeks of this class those along said of announcements but pixel everyone for coming up that area that's get started on the actual the new material and I want to talk to you today about Tibet ,comma tutorial approaches burst and I'm going to pick up on the last slide that I showed you last time and to make sure that it's skim through it so quickly that it didn't make any sense to you and then will go on to the next topic OK case last time
oops I was talking about
Modular Architecture in organic synthesis is a what what I wanted but the give me 1 moment to figure this out I guess will live with this guy and so on modular architecture is a design principle that allows you to synthesize compounds in a way that allows access to ,comma tutorial libraries and last time we talked about this principle of cometary were libraries ,comma Torah libraries are big collections of different molecules and in ,comma tutorial library you have a different set of modules that are shuffled around and recombined in a way that makes a whole series of different molecules OK and we talked about last time about this class of compounds called Denzel dies if he had this name should be the name classic compound in the vaguely familiar to you this is reporting class of compounds that's found almost ubiquitously in medicinal chemistry and the use amongst other things the entire depressants and so you could make a commoner library of the based upon this spends days he'd scaffold by varying the or functionality shown here and you can do this by a very straightforward synthetic plan that involves the recombination of a power of AI could a teetotaler together with the panel and so this is a compound has been key Quito and Adelind functionality together can add some sort of help heal he lied and an acid let's just say acid he lied and mean and so these also not together to give you this benzoate appeared framework and that show you the mechanism for lesson is not so important for discussion skip over but you can imagine having say you know 20 different versions of this key talent base compound with different are ones indifferent or to lose 20 odd threes over here .period 20 compounds that have different our 3 and then say 825 compounds that have different art forms when you put this all together and you would do this in individual reaction flask you'll end up with a large number of different compounds OK so that is due 2020 20 pesos 20 of these 20 these 20 of these funds if we make all possible combinations of those how many compounds will we end up with how many bands of appearance 2010 mostly because 22 the 3rd of which it is it it doesn't thank you OK that's a scary enough OK so 8 thousand compounds can very readily be synthesized by starting with the it's simply 60 different of precursor compounds and that's pretty powerful if you at 8 thousand different bands that I opinions each 1 that is potentially some buyout activity then I'm back collection could have a lot of very powerful a new therapeutic compounds that for example OK and we talked about some other different modular framework 2nd now I want shift years that's the example of using that ,comma tutorial chemistry at the end of this synthetic laboratory this principle of course borrows heavily from biology and it turns out that European system uses a
similar principle to develop diverse molecules called into bodies which are 1 of the 1st lines of defense against foreign invaders OK so if heaven forbid you decided to come take the apple up off the ground over there and started chewing away on it and you would find a lot of foreign bacteria that Apple and so on and likely likely on into bodies would play some role in fighting off those foreign bacteria OK so here's the way this works so in the body's job is to be binding proteins their job is to grab on to non self molecules so I'm going to refer to this classic compounds as professional binding proteins that's what they do for a living in a cave that so their professions and on it's 1 of the new systems 1st lines of defense structurally they look like this I told you about earlier from 1 convention for looking at protein structures looking at using a ribbon to trace out the backbone I did tell you really want these errors mean companies curlicues will get to that later but a different convention Pellecchia protein structures just maps surface onto the outside of the protein structure a case of you were able to have you know special electron microscopy eyes you know eyes had amazing power resolution and vision ability with the at the bodies really will look like is something like this because they have a sort of bumpy exterior now this stuff down there and I've colored this into body to highlight on its structural components OK so into bodies it turns out are and are composed of a total of war chains 2 of these chains are called light chains they're shown up here at the at the top ingredients and then this sort of sigh and color on and this purple color and and then there's too heavy chains have the details not so important that get worked up about memorizing how many chains each protein has here's what's important to take into bodies have evolved a mechanism that allows them to recognize diverse binding partners and they do this and by having a series of flexible loops that can accommodate different shapes that they need to bind to OK so I'm turning out to the very tips that to the top of the antibody body up here which is labeled binding site this is where the body will try to attempt to bind to that foreign invaders let's say you picked up a virus when you bit into the Apple now the viruses floating around your bloodstream so that into bodies .period attempt to bind to the exterior of this virus and if we Izumi in and over here this is the tippy top this is just the 1 this is called FAB region of the of the antibodies to the fabric to land value over here and you could see and then in this theater roles here this is an antibody binding to a small molecule so it's pointing to some target the exact target not so important for us but notice how the target is cradled in these loops table loops are gripping this body very gently but it bit but sided with repeating this antigen gently but the intention is fully buried in these loops so these loops are flexible to accommodate many different potential binding partners that flexibility is critical that means they can recognize you know virus wanna virus to working good Ethiopia pick up some totally different viruses they also think that 1 up to hook you hope and on at the same time these provide enough other types of molecular recognition which will talk about later that allows strong enough binding to muster an immune response and then the antibodies basically sound alarm the redcoats are coming and then get the onion response to go into high gear to start killing off that foreign invaders 10 so very 1st line of defense against foreign invaders now the problem and the big challenge is that some of these antibodies need to recognize stuff that you're so you're nearer human organism you I have never seen in your life OK that means that if you travel to India you travel to Ohno of the palace freezer wherever it is if you travel and you pick up some new organism or some new foreign beta enter body there ,comma a library of antibodies needs to be ready to recognize that and of course of you know this stuff has never been seen before the never trained on that so that about this strategy that union system uses is to have a vast collection of potential binding partners OK so make a big collection of different and bodies each 1 with structural differences to be ready to recognize any particular 1 type of data OK now here's the other thing so the size of the
collection is huge occasion these antibodies are produced by immune cells called T-cells which look like that's so 4 B lymphocytes this collection is a fairly enormous it's estimated to be on the low order of about 10 billion or so different bodies OK but earlier I I told you that the and human gene it is only about 20 4 thousand genes price so obviously there can't be found 10 billion different molecules in the system at each encoded by its own gene so instead the strategy that immune system has evolved is a strategy whereby different gene segments are recombined in a way that then produces a comet or a library of different antibodies OK so let me show you so there 40 of these variable genes the module's 25 diversity model 6 joining models and they're shown here so here's the Devedjian said energy and then bye ,comma tutorial did it ,comma tutorial Jean assembly these are brought together to encode the antibody heavy changing OK so that encodes the heavy chain that I showed on the previous slide similarly the light chains are produced by another type of common at Oriel Jean assembly whereby 1 of these visas picked out and etc. One of the Jesus picked out etc OK so in doing this you can get a theory vast library of different antibodies furthermore the into body diversity pool is further diversified by I'm a series of genetically relations that includes 1 variable Jean joined so when the genes are joined together they're not sort of glued together neatly instead there's little parts that are clipped off or added and then furthermore there's a process called Type mutation that goes through and I am makes tiny little mutations in the coding sequences as well so in it and you end up with around 10 billion or so different and 2 bodies each 1 different structurally and potentially able to recognize whatever foreign invader you happen to counter during your life it makes sense OK so to summarize what we're saying is a strategy for ,comma twirl synthesis that's used the laboratory and also used by your ourselves OK in both cases there are these modules that are shuffled around and then rejoined them in literally random fashion to give us a vast collection of different molecules and then we hope that these different molecules are going to be functional when the time comes that we actually need them it makes sense to take their question over here we used to call there's so many of you know some of them against those of OK yes so there's a separate processors who tracks out things that recognize self as well yeah that's interesting question as well so there expressed wish Joshua because OK
changing gears and so the last topic in Chapter One is a survey of the tools that we need a chemical biology to be able to address problems and address the frontiers of chemical biology so I'm going to have a very quick survey in the next 15 minutes or so I'm going to share with you a series of different tools that you can then use in your proposals a place that they could as you're trying to put together a tool and this is going to be the hammer saw the nail gun whatever OK so these are the things that you need to and but to address to design experiments a chemical biology OK so again this is useful for planning your proposal Siemens 1 but this also provides a toolkit for further experiments were going to be referring to this toolkit quite a bit in this class so later in the quarter albeit that say Oh yeah you member those into bodies that I mentioned earlier and those are now going to be a and this kit is very diverse and vast and it ranges from chemical reagents to the entire model organisms and there's a huge amount of diversity and in the in that in that range of different tools so chemical biology as a field uses all kinds of different techniques it uses techniques for molecular biology at uses techniques from the very latest in nonlinear optics and into image sells them and everything in between OK in addition I also want you to know these tools because I want you to altered design experiments on the fly to determine you know X became a very common mid-term question for me would be How would you design an experiment to address you let in what kind of us signaling chemical signaling is being used by the gut bacteria your gut bacteria to too let's let them let their neighbors that sugar has arrived occur such as a pretty interesting question and want to know whether you you do that on OK in addition I want you to know how to describe negative and positive controls were going to be talking about experiments and all the experiments have both negative and positive controls so when we talk about that topic 1st a pace-setter going to be designed experiments you need to know 1st when a negative control is and what a positive control as it is you need to be altered designees into any experiment that you want to design OK so good experiments have both positive and negative control positive control 1st as a positive control is a set of experimental conditions that provide expected resource response were a positive result OK so in this case you could basically wanna know does the conditions in my class produce in the ghetto prepare produce a amplified DNA or something like that and so what you'll do is I'll start with a on sample that you know should work a certain way and your experiment OK it should give you a predetermined result and it should be completely consistent every time it should be very itchy give you that expected result every time so this tells us that our experimental apparatus is working at a need to know this because I'm oftentimes experimental apparatus in chemical biology labs isn't simply a stir and you know hot plate reading just test hot plate by sticking your fingers on a for a nanosecond of the chemical apparatus might be you know a tiny little migrant migration a fugitive and even you shot and a bunch of different reagents unit tend agents all of which are clear none of which you can really assay all that readily so what you do is you set up a set of conditions where you know the results and then you see that we can result is read capitulated under experimental conditions present this as a positive control and you always want to have 1 of these good experiments have positive controls good experiments also have negative controls so this is where you leave out some experimental conditions in your experiment maybe leave out the test sample OK so earlier I was talking to you about them trying to assay but let's just say I'm some sort of microorganisms found in your stomach that responds to the presence of sugar OK and maybe you want to know how and whether that microorganism releases in all the signal to its neighbors can't just about experiment so you're experiment your experimental apparatus will be measuring the concentration of it all your positive control will be say some bacteria that you know releases and all and that tells you whether it's from his working the negative control can be entirely missing the bacteria because you do the exact same experiment but you will need not the bacteria and no in Dole should result if you see and all resulting that tells you that you have a problem that tells you that's you have a say in contaminant for example this should result in a failed experiment on negative results so it's experimental condition missing a key element say the test sample the thing that you're trying to test case and again it should result in a failed experiment if it does not result in a failed experiment that tells you that in your conditions you have some sort of source a contamination you absolutely need these negative controls OK because all too often a chemical biology we have lots and lots of contaminants and there are lots lots of false positives and we just don't like that kind of thing you want to know that if you're going to tell your friends down the hall that you discovered on a new basis in the the DNA sequence and you wanna know that actually that's the real thing a credit unit that telling your good friend US-Soviet turns out to be totally wrong later and makes you look stupid because no 1 likes look stupid but now because we have very complicated experiments a chemical biology that involve lots lots of variables remember I told you earlier about the 1 that has 10 different things thrown into little tiny Microsoft fugitive we often have multiple negative controls 1 for each possible variable OK so for example you might read out the magnesium from the buffer just does the magnesium contributed to this experimental results you know is it's actually a magnesium dependent enzymes that produces in as expected if you and if you leave out the magnesium and use Diller getting some result that could tell you that maybe it's not a magnesium depend process Case a negative controls and tell you a lot about what's going on in your experiments good experiment should have both negative and positive patrols the questions about what positive patrols are went negative controls are yeah and you OK this is a great question it happens to me all the time OK so the question is what is your name b the focus of these questions is if you are a positive control fails and you negative control works wonders that tell you about the experiment I would say that that tells you that your experimental conditions are worthless and you cannot interpret the experiment OK because of the positive control fails to work then you really don't understand what's going on in your experimental conditions have had a positive control really tells you whether or not you understand all of the elements that compose your experiment if the negative control fails as you expected it to fail well maybe it's failing because the positive for the same reason that the positive control failed maybe you've left out some key
region right you know maybe I unit heated up to the right temperature and hold it there for long enough for something so both your positive control and your negative control have to work in order for you to interpret the results at town being really dogmatic here I will tell you and I will tell you that we scientists oftentimes look at experiments that don't necessarily have every control working OK all look at those mice socially those all the time folic on but I'm not going to you know call up there and you know the Nobel Prize committee in Stockholm and tell them about it OK because it's probably not worth a lot of time but will use that to guide the next set of experiments will say Well what is it that the failed in the positive control animal will design and troubleshoot and designed the next experiment using that information will look at the negative patrols earlier that fill that bill that failed to these variables are probably OK what about this 1 account so you can get a lot of information from experiments that failed in fact you actually to be a successful scientists you need to learn how to work with experiments that failed because 90 per cent of the time they fail intent but you know that's the way life is so and you learn as much as you possibly can and then you move on but which to to make strong conclusions that you need experiments were about the positive control and the negative control or working as expected OK good question the how other questions the riots and reshape example let's imagine that you wanted to amplify on some DNA sequence using a technique called PCR details not so important now hopefully you already know what PCR as I understand it's taught in high schools now if not you can look it up in the textbooks and if not don't stress about it all talk about PCR later and later you'll need to know how this works for now let's just use it as a method for amplifying DNA and furthermore here's a method for visualizing DNA as on a jail and I know what you have done Teal c This is kind of like TLC except that I'm Banzer upside-down repair but it's more or less it's like upside-down Teal c the same technique that used to visualize compounds except where visualizing DNA by running it through an agarose gel again if that technique is not familiar to you don't panic will talk about that later in this class and for now we have a method for amplifying DNA will method for visualizing the result Indiana pay now heroes are positive control it's the lead over here that's labeled with a plus a case over here is a set of conditions that you know results Indiana and notice that there is a bond rate here in brightly at a pace that tells us that our positive control works you have a sample of DNA that you know should be amplified under that set of conditions and lo and behold it gives you that nice break their necks Lane the next Lane are the negative controls OK so we don't see that same bands and say that is missing the DNA samples OK we don't see that same down so we don't have to get worried about it final Maine this is our experimental where he do these 2 experiments the positive and the negative control just to see whether your sample over here is working OK and here is the 1 that has the actual test sample and noticed that gives you DNA and it turns out technique separates on the basis of size it gives the DNA of a different size OK so we have both a positive control that works as expected we have a negative control that works as expected and then we have our experimental expect 1 In the a typical experiment in my lab will have 6 or 7 negative controls may be too positive controls just so that we know what's going on we don't we cannot visualize what's going on so we need all of these controls to and follow what's actually happening in the in the test it's a pair sometimes even smaller than test it's sometimes down a single molecule level so we really really need all these controls I want you to be thinking about these controls when you design your proposals paid good proposals will have both positive and negative controls how you design your experiments in how you discuss them with me Malone and determine how creative they are and how often and how robust they are and how likely they are to stand up to scrutiny OK if you want to propose something is totally wild like enough time travel or something like that but I will discourage you from let's see what a propose something that's not quite so while OK but you come up with a whole bunch of controls that will really tell us something about whether or or not you experiments working I'll go with that occurred so b as creative as you possibly can be effective I look forward to reading the erect and let's talk about tools so the 1st tool that use quite extensively Chemical Biology Laboratory involves dies better turned over to the surround the color metric indicators as the as the tournament and have been used for hundreds of years probably least 120 years in chemical biology experiments for all kinds of things used to same Stout cells they used to follow enzyme reactions and on here is 1 example of these diets if you have some sort of enzyme in your reaction that you're trying to do assay an enzyme somehow Cleaves this month ether bond and what will happen as this will then release a feel and nature of being a late molecule shown here this nature of being away is a nice yellow color place you can very clearly see this 1 is clear this 1 is yellow pacing around to see the difference in case of enzyme is present enzyme functional you get a nice yellow color from the the from from this solution OK now on this this is really powerful OK this gives you a way of turning stuff that you can't see into stuff that you couldn't visualize OK and furthermore this is typically quantitative and other words you could pass out white through here see how much like it's absorbed say pass and visible light through here see much like it's absorbed and use this to quantify how much enzyme is present in your solution they doing this gives you a really effective way at addressing things like enzyme kinetics that you know different properties but you can look at a finding between receptors in my against using this type of technique so this is bread-and-butter of chemical biology labs had the other question so long that it is on OK yes sir this question is how do I know the concentration of the enzyme in this reaction how you make a quantitative OK so what you would do is you have a series of controls we have a known amount of enzyme that's turning over this dies and you see how yellow jets after 5 minutes with at noon quantity of of enzyme occasionally could use that to calibrate this experiment so yeah so the subtleties to everything I'm telling you what this solution to our thanks for asking other questions OK so in this example were looking at like that's absorbed and then I this absorbency results in the molecule radiating out the energy that's the of the photons as deserving as heat came a different experiments the light is absorbed and instead of the energy of the photons being
radiated out as she instead it's blasted out by the the molecule as a phone with the lower energy OK so it has a different wavelengths of light that's been given off OK so here's a series of different molecules that have that property in that the absorbed photons and then read it back out photons of lower energy use used in fluorescence experiments extensively chemical biology user used to visualize molecules inside cells inside organisms and Donahoe a whole host of different experiments OK sorry told his quarters absorbed photons of light and emitted photons at a lower wavelength came on new can select a year in Europe might in Europe microscope just those photons at that lower wavelength by setting up a filter OK so the way this works is if you're on the floor for a let's say this of flossing over here said here's a floor for it's going to give you this greenish colored light and in microscope you will have a filter that filters out all the lights cases bourbons backscatter except for light of this way of life that is this nice green color that will give you exactly where this glossy molecule is binding inside the cell have furthermore this technique is extraordinarily sensitive it's 1 of our most sensitive techniques in chemical biology and supplanted only by the thing that Miriam is working on a proposal Miriam is doing something it's going to be even better but for now up until say 2 years ago this was with the champ and I you can get down to single molecules under the right conditions using fluorescence you can actually see 1 fluttering away as it's releasing photons they pretty amazing and I will tell you that those right conditions completely nontrivial OK takes cooled and CCD camera that's very very large and very expensive this is not like you're your cell phone that's hooked up to the top of the microscope is the release kind of a very special type of camera to visualize the sort of thing and plop enough employment but in the end this is really powerful stuff because EPA visualize just 1 molecule inside the cell that he could start getting a processes that they're really govern how cells work where cells are often times and responding to a low number of molecules inside them so this is a really powerful technique it's used for all kinds of things in this example I'm showing you to cells that are dividing and they're being pulled apart by the scandals at over here outside the DNA in blue it's been sigh and is being pulled apart by the spindle apparatus into the 2 daughter cells and then act and which is that the protein scaffold the Basell kind of that the skeleton of a cell is is highlighted in red over here they actually spectacular stunning images relayed on which you can find examples of where this technique is used this is completely ubiquitous this technique is used for visualizing stuffed inside the cell is used for visualizing stuck outside the cell in little tiny reaction flask for doing screens of drugs and for doing the typically assays of cells as well OK question over here yes to the single-molecule technique that describe would use the threat of picturesque and other questions yes over here in this the question on chassis of the Phillies home the remains and this is cool Chelsea's question is a really good a said Chelsea asking you know why should you know this blind to the DNA over here and nowhere else inside the cell leader will be talking about the dyes that bind to DNA what makes them special but actually rightly the need some way of getting guided into the cell so for example these active in that the red color of act I think he is it onto body that binds to act in a case that's the big molecule they showed earlier that enter body is then attached to this wrote me a case of rotten attached to the end embodies the antibody body it's been used as specific practice it .period stacked in it's a professional binding protein that was raised just bind to Acton and now it's going to highlight all factored in the cell in this road mean of red color over here that really cool stuff so thanks for asking but you have to have some other technique that will target the floor for specifically to what it is that your lighting up inside the cell had requested Chelsea other questions OK so again totally ubiquitous technique used very extensively I every single 1 of you will have some experiment in mind that will use either fluorescence 6 passes for color metric assays of your molecules cannot use the deal we can expand these up I've shown you 2 different assays we can expand these up to look at literally thousands of molecules that day and thousands of conditions a day using and abusing for example micro tighter plates case these are plates that about this big so they're not that big and the standardized and they have a standard number of wells on them so the ones my lab uses are 96 or sometimes 384 wells plate that's as big but it's not unusual to have wells have 1536 wells in a little space at about this big repay were each well it you know take 10 micrometres or something like that OK but that what that means that it is on that plate you can pass a 15 36 different conditions of cases 15 hundred different editions can maybe 50 of those are different controls negative controls positive trolls but you're still looking at a huge number of different molecules of different other variables that testing in that 1 little tiny area end of them it's not infrequent 2 for me to visit places where they have a whole room the size syllables of robots that are and pipe heading that that this technique over here pipe heading on an automated fashion regions into these tiny little plates and then the robot has like a little you know on that and brings into a reader and observances and read out automatically in all this data is important to your desk and appears on your laptop and very cool so guess it's a it's a great time to be alive OK so this observance we talked earlier how it can be used for quantitative analysis oftentimes you rely on in 2 bodies to bind with specificity to a particular molecule this is the question that Chelsea was asking it's not unusual for us to actually and Anthony into body that specifically some target inside the cell OK and so we're doing this so that we can actually look at just that individual protein and I showed you earlier the structure of antibodies that structure allows them to be very very specific if the antibodies attached to an enzyme that you can look good turnover of a diet and that can be that can visualize the presence of the molecule as turnover of a diet had a run so I think it makes sense can the scope of this is enormous and pharmaceutical companies will screen through million compounds in 2 weeks using techniques like this 1 case in there might be to humans that are involved in those experiments show the whom achieving the regions in the robot happy there turns out actually programmed the robot not as traditional so you know it's very different telling undergraduates would pipe that all these things OK this is much more industrial-scale vanity is very timely loves some by this move on 1 another very
powerful technique and that she is quite routinely is basically a Darwinian evolution technique where you can evolve organisms that can accomplish some chemical goal for example over here this is an experiment to find mutant bacteria that can take advantage of fire and metabolites aspiring so in this plate over here this left side is the negative control these are bacteria that you don't expect that were not mutated and on the right side so you don't not expect them to be able to handle iron and on the right side these little little circles are examples of the colonies of bacteria that can take advantage of fire and actually accomplish their metabolism on the right side gears and be panel B this is a different experiments we're looking for bacteria colonies that can produce lycopene lycopene is the red dye that's found in and to me that's the reason why tomatoes are red and it also is thought to have some anti-cancer properties although that evidence for that is not as well supported but in any case you can imagine evolving the bacteria and putting in the genes that encode lycopene production and an evolving the bacteria to produces this red color dye and then at the end of the experiment you go in and simply pick out the readiness of the colony's over here now you look closely at this there's some really really really interesting stuff going on pay due notice how some of these are kind of modeled in appearance this 1 has some little red dots and it looks mainly clear what's going on there that's absolutely fascinating OK I'd like to know more about that so the essence of being good scientists is not simply running experiments the essence of being good scientists is designing good experiments and then observing the results like a hawk OK you have to look at these things intensely intensely intensely and ask questions why is there a white halo around this 1 and then a red inside what is different between the bacteria here and the bacteria out here maybe it's a trivial reason maybe these guys have more time to produce the lycopene and these guys are just you know they they haven't grown as long and outside but you still would want to know that and so being a scientist is all about designing good experiments and then next observing observing observing in making those observations that's where we make progress in science and where we make progress in chemical biology of somebody but so
I did tell you about the Darwinian evolution you can imagine getting a bunch of units taking out the winners over here mutating them again picked up the winner's mutate again pick up the winner's that's the same process of evolution that we talked about on Tuesday we diversify the pool select for fitness keep doing the same thing again and again and again until eventually you have some super growers 1 2nd row really really fast under those conditions and that would be really interesting to understand at a molecular level what's going on there and what's allowing them to do that became viruses are
very powerful tools for gene delivery and the very efficient and affecting cells all the show you an example of viruses in action in just a moment of my laboratory grows large quantities of viruses as a tool for chemical biology and their good-natured goal in life is to make copies of themselves that's what they did appear to have a very short lifetime and during that time there totally fixated on making copies of themselves and because they have shipped such short lifetimes and they're so ruthless that it will find themselves this provides a very powerful tool for selections take me show you want an example of this
example is using a technique called phage display which again is supplied by not my laboratory and many others on what we do is we start with the filamentous virus OK so each 1 of these little hairy things over here at 1 of these threats like things there is a single virus and of the virus this particular virus infects equalized so like all viruses the inside of the virus is in encapsulation encapsulates the genetic material In this case this virus encapsulates the DNA there's other viruses that are on a base this 1 happens to be Nunavut canine here's the great part as a chemical biologists we can go in and and manipulated DNA that's found inside the virus when we do this we can coax the viruses into producing large numbers of different viruses each 1 with a different protein displayed on its outer surface pay each 1 with a different protein outside on its outside OK that's called this way OK and then you can do selections so for example you have a say a billion different viruses each 1 of the different protein displayed out here you can then throw these viruses at a chemically modified surface down here and then simply take out the winners the ones that can grab on to this chemical found on the outer surface over here everything else they can grab on is washed away you washes away using some sort of buffer a case just low water over and over this for 5 minutes I guarantee to everything that's a week Binder everything it can't really get a good grip on the chemically modified service gets thrown in the bin the trash OK and then you start flying up those winners and then you do the process again and then you do the process again and again like 4 or 5 times by doing that you start to get very tight blinders on to this chemical found on the surface of your better targeting OK so this is a way of starting with literally 10 billion different molecules and coming down and identify just a few that do something special such as blind to this chemical over here said question of you University yeah yeah OK that's a great questions ahead even manipulate these viruses so what we do is he in fact that the Ecole lighthouse and then we can be colonies of those Nikolai that affected reach colony has won only 1 type of virus inside of it a and you can actually see the virus there OK this kind of violence in the media yeah yeah let me show you on the next flight OK OK so the question is
about the particulars of how this technique works again fears the virus over here and but here's the size of our library that's around 100 billion or so that's the maximum size that we can make the notice said this and this electron micrograph over here and there is a little cluster of grapes at 1 end of the virus that's its head that's what uses to grab on to the coaliton going to infect OK so that's this part appear a paid that's the head of the virus that great and again the DNA is is is and stuffed into a long pipe a virus over here and the virus is very flexible cases virus is like a hose in terms of its flexibility now here's experiment that I was getting asked about earlier so what you do is you make your library of different viruses each 1 of the different protein displayed out here and then you throw those viruses that some target packed will occur this package a target that happens to be stuck on the surface of on some sort of service OK you then select all of the things that bind to pack and wash away everything it does invite OK so in this step you go from 100 billion down to just say Let's say a couple hundred candy and then you pick out these viruses you amplify them up in their host the collided and then you do this again OK so again we target packed them wash away the non-binders amplify the binders wash away the non-binders amplified binders and just keep doing this a bunch of bunch times pay at the end of a joint of assailants 858 100 that bind really well to the targeted Pac-Man shaped molecule OK so now you want to go on anyone a look at those individuals and see which 1 binds the both the best and the better question right OK so what you do is you in fact the winner is into the call life this is a bacteria and then you are and you can plead out bacteria such that you end up with colonies because that was
shown over here each 1 of these doctors is called The Colony is a genetically identical bacteria In the case of the virus infected bacteria each 1 of these colonies will have a different viruses and a different bacteria Fagen kind and then you
can assay each 1 of those individually it's OK it turns
out that this principle of vast libraries of proteins that are displayed on stage is also applicable to DNA and RNA and this is another tool that use routinely chemical biology laboratories and so my colleague Professor Andre looked at for example routinely makes huge libraries of RNA and then selects reminders from this big library so I'm here for example is a derivative of road a molecule they showed you earlier and here's an ornate for us sequence that likes to bind to this and wrote mean like molecule that I showed earlier so you can select for binders to all kinds of different things from these vast pools of both DNA and on take using exactly the same principle showed earlier you attach this molecule to some surface you throw at that surfaced the big pool of say on a wash away all the non-binders grab onto the binders amplify them up and repeat the process case it's simple molecular evolution exactly like the evolution the talked about on Tuesday not the reason why this is important but it important applies evolution is you cannot know in advance exactly what sequence is best .period to bind to some complicated molecule like this OK I know so it would be really cool I could sit down on with my laptop and you know crunch some numbers and that and that get the perfect already sequence but we chemical biologists can't do that OK we just don't know where the design rules for designing something out there that has a pocket shaped like that and furthermore whether the functionality so we're going to need that will be complementary to the part of the partial positive charge every year on the lone pairs and oxygen the aromatic over here etc. and it's better just to go out and do the experiment and just see what you get and then analyze what that what you get at the end of it it makes sense OK so that was an example in your tool kit of using libraries both on phage libraries that a DNA or RNA and the next thing in your tool kit of are small molecules so small molecules are
used extensively in chemical biology so some of these molecules are antibiotics some of them are natural products that are found only in there being produced by microorganisms as they fight off the invaders but others have discovered a chemical biology laboratories with a particular function and so on these molecules are used quite extensively but in chemical biology laboratories but also cell biology and biochemistry let's so for example and yesterday I showed you the pathway of of the central dogma which is the information pathway from prior synthetic information inside the cell and small molecules such as the 1 shown over here are known to inhibit pretty much every step of this pathway and so on on the shelf you can molecules that would say disrupts the process a translation of life cycle had submitted shown here and other molecules that disrupt transcription such as this managing amenity offer amenities shown here and these are molecules which can buy from your chemical supplier said to the small molecules give you tools to shut down specific events inside the cell OK now what so powerful about this is you can control the day the location of the time delivery etc. with perfect control over those type of things OK the doses simple regular the exact concentration the small-molecule you want and on where this is important is that also controls the per cent of innovation that you're doing OK so let's say you want to shut down a little bit of protein translation but not all protein translation maybe you don't use a huge quantity of cycle had over here but maybe on the more likely that you just wanna shut down all protein translation so you add a large concentration of cycle hacks that in addition you control location so you can deliver the molecule to on some space some a looking at an audience under the microscope in you wanna know you know what happens if I shut down protein synthesis on this part of the stomach but not this other part every year you could dose that for the stomach and leave the other part on dosed and addition you can control the time of deliberate delivery right you can say look at security of circadian rhythms inside but I know inside your neural cells right circadian rhythms of the timing of clocks that that is used by organisms to coordinate the day you might be really interested in knowing what happens if I shut down the transcription factor that right before the organism goes to sleep so being able to have a small molecule the precise time in a precise location and with the precise concentration is really powerful as 1 of the reasons why small molecules are so important inside cells inside Chemical Biology of cell biology labs OK any questions about what we've seen so far OK I showed you a whole series of different experiments that you can give you any should you can plan to do and I want to show you next other players that you're going to be using for designing your proposal idea it's OK you're
going to be using model organisms because as I told you earlier I don't want you to plan experiments on humans because that would not be that the point of this course OK and instead what I'd like you to use is a model organisms or samples that are obtained from consenting human adults OK I'm OK said in general that when you're choosing a model organism he wanted choose 1 that grows easily and that it's easy to study the grows quickly and has some relevance to human biology and not every model organism is going to be so great if you're on 51 a study say you know the hearts of Burmese pythons and Burmese pythons take years to grow or something like that but it might be a very long Ph.D. for you or your students and no 1 likes that a case you want organisms that grow quickly that inexpensive to grow that don't require really exotic conditions to grow fear for have you have to figure Burmese pythons rabbits every 2 weeks or something like that it's going to be expensive and is also a mail on a parcel and see you need to have some really good reason to have chosen Burmese pythons as the model system in general and these are the model systems that we used in our chemical biology laboratories with the exception of humans down here I'm just listing for 4 point of comparison OK so we will will march to Oberle stepped through each of these and tell you about the properties of tech support example I've shown
you earlier on use of this bacteria PG This is a virus that only infects the collide bacteria and hence the name bacteria fades so it's a virus that eats stage means to eat bacteria and this only affects the equalized this makes it very convenient for used in laboratory we don't have to worry about if it escapes quote-unquote escapes and not to worry about an affecting my co-workers the Protestants oppose stocks in the lab and furthermore it has a very simple to it just has 11 genes and gene and that makes it easy to manipulate a K this reference here is to the picture that I'm showing you and I showed earlier in the class it's electron microscope pressure on In addition it grows in equalized Misha you with
people I look like so here are some of the whole life next to a red blood cell since this right now outside this next to a Mac macrophage cities of the the US cells in you in your immune system that are charged with beating the collide required or other foreign invaders OK so each equalized on the order of about 1 micron maker meter in scale and each human cell is on the order of 20 to 30 microns in scale His 2nd he kind of idea and I think this picture dramatically illustrates a relative skills this makes sense Radikal I opera periods should be structures appear periods last time on human cells of course so you carry out excels under a lot more complicated they have a lot more and organelles inside them etc. OK so classic experiment in I'm in while it biological history and this was this is Griffith I'm at the top part that's Fred Griffith at the top and with his dog Bobby was selected over the names of scientists dogs but regret this learn to recognize aura of pneumococcal and differentiate them from pneumococcal so are equals rock as equals smooth and he found that did yes pneumococcal I could transform life and on the very this guy down here and working at Rockefeller showed that if you isolated DNA from the dead S bacteria it could transform but all are bacteria into best OK so the important ideas there is that it showed us that DNA Was the hereditary unit of the cell that DNA was encoding the machines inside the cell there were making the outer surface either the the smooth or rough the sad history here as a friend with it died in the when the Germans were bombing London he died in London blitz OK so call I extensively extensively used section you couple examples including phage display today on Easter used as a model system for very simple but you carry out and said you know equivalent to the procuring you've got the call I but very simple to grow very easy to genetically manipulate etc and as things get more complex we get words organisms like fruit flies over here on fruit flies used extensively In laboratories because they grow quickly and you can do selections for things like the morphology shapes of wings and things like that but they even more complex traits such as behavior and I will show
you 1 example of that this is 1 of my all-time favorite examples this is a great already have people lined a professor at UC and in this experiment but the Haber line lab has built an apparatus of the and a Newbery Honor OK so this looks set to run through flights case here's the way this works this fall over here contains ethanol and then she pulls a little bit of a vacuum on this so that the vapors ,comma Archie below 0 over the top of this so that papers of ethanol come off over here and then she applies a bunch of different from flying units to the very top of the the column when the fruit flies land on these columns over here the consummate like a little wire the fruit flies grab onto the state's OK that's what provides like to do the right to perch on things but now they're being washed over with this ethanol vapor alcohol is coming over them and they're inhaling it can get away and so as they start to wobble back and forth they fall down to the next and cold and then they grab on again but then they start wobbling around as they get shrunk from ethanol and they drop down to the next 1 until eventually down here they they totally Parcells now down the wild-type fly over here takes 20 minutes to come through this column whereas here units that that that he reliant laboratory found that only took 10 to 15 minutes to get through the column in other words those were fruit flies there were getting drunk and passing out faster than the other fruit flights to the chemical biology pods experiment would be to understand what genes are involved and then at the key that level of Hamza Bonds why those genes are making the fruit flies drunk faster OK now I do have 1 request please do not plan your chemical biology proposal using Anthony Brianna I've seen every variant of this with marijuana smoke with all kinds of the things that cause all kinds of interesting effect so use any other experiments but what I like about this as I love the do experimental design it's very straightforward anyone if you in this classroom could lamented that and that's what I'm going to be looking for when I look at your proposals and later in the quarter OK I'll see you a week from today back in this lecture hall we talk about 1 model systems and will talk the talk about
Werkzeugstahl
Chemische Forschung
Azokupplung
Chemische Biologie
Replikationsursprung
Mähdrescher
Allmende
Topizität
Biologisches Material
Chemische Forschung
Chemische Biologie
ISO-Komplex-Heilweise
Zellwachstum
Hydroxide
Stammzelle
Werkzeugstahl
DNS
Chemische Struktur
Membranproteine
Reaktionsmechanismus
Menschenversuch
Chemische Bindung
Säure
Molekül
Gletscherzunge
Funktionelle Gruppe
Systembiologie
Terminations-Codon
Enzym
Biosynthese
Aktives Zentrum
Biologisches Lebensmittel
Fleischersatz
Organische Verbindungen
Tiermodell
Wasserstand
Fülle <Speise>
Biochemie
Quellgebiet
Durchfluss
Topizität
Erdrutsch
Wasserstoffbrückenbindung
Tumor
Chemische Biologie
Organische Verbindungen
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Topizität
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Explosivität
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Erdrutsch
Werkzeugstahl
Chemische Struktur
Sense
Reaktionsmechanismus
Chemische Bindung
Alkoholgehalt
Lactitol
Chemischer Prozess
Chemische Forschung
Biologisches Lebensmittel
Pharmazeutische Chemie
Single electron transfer
Chemische Reaktion
Aktivität <Konzentration>
Modul <Membranverfahren>
Potenz <Homöopathie>
Mähdrescher
Base
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Benzoesäure
Präkursor
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Thermoformen
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Sammler <Technik>
Allmende
Molekül
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Idiotyp
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Karsthöhle
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Aktionspotenzial
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Gefriergerät
Zutat
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Membranproteine
Sense
Reaktionsmechanismus
Sekundärstruktur
Sammler <Technik>
Antigen
Allmende
Molekül
Beta-Faltblatt
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Biosynthese
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Immunozyt
T-Lymphozyt
Fülle <Speise>
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Potenz <Homöopathie>
Setzen <Verfahrenstechnik>
Torsionssteifigkeit
Erdrutsch
B-Lymphozyt
Gen
Assembly
Bukett <Wein>
Farbenindustrie
Kettenlänge <Makromolekül>
Chemischer Prozess
Biologisches Material
Enzymkinetik
Chemische Biologie
Blitzschlagsyndrom
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Chemische Reaktion
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Stout
Konzentrat
Einschnürung
Magnesium
Chemische Verbindungen
Lösung
Teststreifen
DNS
Werkzeugstahl
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Nobelium
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Fülle <Speise>
Wasserstand
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Quellgebiet
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Bukett <Wein>
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Chemisches Element
Dictyosom
Chemische Biologie
Screening
Chemische Reaktion
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Kernspindel
Chemische Verbindungen
DNS
Bindungsenergie
Rauschgift
Chemische Struktur
Fluoreszenzfarbstoff
Membranproteine
Baustahl
Sense
Pharmazeutische Industrie
Elektronegativität
Zellzyklus
Anthrachinonfarbstoff
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Molekül
Enzym
Reglersubstanz
Pipette
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Filter
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Interkristalline Korrosion
Krankheit
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Chemische Biologie
Biologisches Lebensmittel
Stereoselektivität
Lycopin
Wasserstand
Fülle <Speise>
Chemische Reaktion
Feuer
Primärstoffwechsel
Künstliche Auslese
Gen
Essenz <Lebensmittel>
Baustahl
Chemische Eigenschaft
Landwirtschaftliche Ausbildung
Farbenindustrie
Anthrachinonfarbstoff
Krankheit
Molekül
Abbauprodukt
Golgi-Apparat
Beizmittel
Chemische Biologie
Stereoselektivität
Mikroverkapselung
Chemische Reaktion
Substrat <Boden>
Setzen <Verfahrenstechnik>
Base
Werkzeugstahl
Gen
DNS
Pufferlösung
Membranproteine
Oberflächenchemie
Molekül
Genom
Pipette
Elektron <Legierung>
Cluster
Kluftfläche
Quellgebiet
Wirtsspezifität
Gangart <Erzlagerstätte>
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Azokupplung
DNS
Bindungsenergie
Grapefruitsaft
Membranproteine
Bonbon
Molekül
Chemische Biologie
Chemische Reaktion
Einsames Elektronenpaar
Bindungsenergie
Werkzeugstahl
DNS
Nucleinsäuren
Derivatisierung
Membranproteine
Molekulare Evolution
Sense
Bukett <Wein>
RNS
Oberflächenchemie
Sekundärstruktur
Molekül
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Chemische Reaktion
Konzentrat
Transkriptionsfaktor
Proteinsynthese
Werkzeugstahl
Tagesrhythmus
Membranproteine
Dosis
Molekül
Funktionelle Gruppe
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Translationsfaktor
Tiermodell
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Setzen <Verfahrenstechnik>
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Phagozyt
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Germane
Gestein
Organell
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Periodate
Gen
Chemische Biologie
Ammoniaksynthese
Wasserfall
Alkohol
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Polymorphismus
Bukett <Wein>
Vakuumverpackung
Dictyosom
Heißräuchern
Ethanol

Metadaten

Formale Metadaten

Titel Lecture 02. Common Tools in Chemical Biology.
Alternativer Titel Lec 02. Introduction to Chemical Biology --Common Tools in Chemical Biology
Serientitel Chemistry 128: Introduction to Chemical Biology
Teil 02
Anzahl der Teile 18
Autor Weiss, Gregory Alan
Lizenz CC-Namensnennung - Weitergabe unter gleichen Bedingungen 3.0 Unported:
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DOI 10.5446/18861
Herausgeber University of California Irvine (UCI)
Erscheinungsjahr 2013
Sprache Englisch

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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: 0:03:11 Our Story Thus Far: Principles to Organize Biology 0:18:39 Modular Architecture Allows Combinatorial Synthesis 0:30:40 Common Tools in Chemical Biology 0:47:04 Fluorophores Allow Visualization of Molecules Inside the Cell 0:52:24 Assays to Detect Molecules in Solution and Cells 0:58:41 Viruses for Gene Delivery 1:02:18 Phage-Displayed Protein Libraries 1:04:55 Vast Libraries of DNA and RNA 1:07:09 Small Molecules Provide Control over Cell Processes 1:10:26 MOdel Organisms for Biology and Chemistry 1:13:41 Bacteria Used to Define DNA as Responsible for Transferring Heredity 1:15:32 Fruit Fly (Drosophilia)

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