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Masters degree capstone option order write for me capstone art class edit my course work on voting as soon as possible ´╗┐dressing for the occasion yes yes I've put on my famous chemists tie most of them all quite a few Nobel Prize winners though a few predate them just about to do the video about the Nobel Prize I need somebody to sit in Diane's office yes it will come this year's prize deals with cells and Sensibility the Royal Swedish Academy of Sciences it's really more for biochemistry and molecular biology and I don't know either of the people but it sounds quite interesting this year's prize is for something that I know nothing about though I can understand White's importance yes sir my name's Barry Callum I'm an associate professor of medicinal pharmaceutical chemistry here in the School of Pharmacy at the University of Nottingham unfortunately when Nobel created the prize he didn't have anything that covered what is now called molecular biology I was really hoping that these guys would actually get this because this is this is a reflection of decades of quality research and so it's right that some of the chemistry prizes should be for that when you when you look at g-protein couple receptors these these are basically one of the key receptors that are expressed in in almost all of your cells throughout the body and they are effectively acting like the lock that a key fits in to open up activity that needs to resign or occur within the cell for your body to function so your body is full of cells like this and circulating through the body are hormones which are released for example when you're frightened and I get booed so one of them most well-known is adrenaline adrenaline is a key neurotransmitter in indeed the work of one of the Nobel Prize recipients Bob Lefkowitz he's his major sort of efforts where he was the first person to actually clone the receptor or the beat Regina scepter the adrenaline acts at within the body and the key point is that the hormones which are quite small molecules can't go through the outer layer of the cell the membrane but instead there are so-called receptors the subject of this prize g-protein coupled receptors which sit in the outer surface of the of the membrane and go through it so when the molecule arrives on this side it sends a message into the cell so these receptors are are the middleman they are the gatekeeper that basically translate the message that that neurotransmitter needs to deliver to the inside of the cell to exert its effect in the Nobel Prize announcement the professor who was talking about this was quite lucky had seven rods because the structure of the molecule involves seven strands which she had quite nice long rods I've only got pens so you can see seven of them then it'll bundle so this is the outside and this is the inside of the cell so when the adrenaline goes into here it pushes the bundles apart because the chains are rigid like my pen then what happens at this end effects that end and the clever thing is depending on which molecule docks on the outside so the insides of the rods are pushed down different amounts inside the cell there are different proteins swimming around and if it split pushed out a small amount this one can go in but if it's pushed out a much bigger amount then this one can go in so this is a computer image of one of the first crystal structures that came out of Quebecers lab this is the human beta to audrina scepter the one that I mentioned that is in the the tubes of your lungs and it resides in the membrane through these these sort of helical units that's where it binds in the membrane so you have the cell membrane here and then the ligand comes in from the top and you can just see in there that the ligand is bound I can sort of just quickly sort of so the ligand is is just bound in here so that's that's about sort of a third of the way down and when it binds in it causes the receptor to change shape and that information is relayed down to the part that is in the pointing to the inside of the cell they are there beautiful structures they've got the from called the serpentine receptors because they weave in and out of the cell membrane with these seven transmembrane regions so it looks like it sometimes we knew you have seen them in a cartoon in a book that you're like a snake weaving in and out now the reason why this is also important is that about 50% of the drugs that you annotate the pharmaceutical products operate have their effect by interacting with these scepters and they're not quite the same shape as adrenaline or dopamine or other hormones but they're sufficiently similar that they will affect just some of the receptors so you can get very selective behavior and treat a pacific condition have you ever met these guys I have met both of them and in fact I'm talking at a conference in Melbourne this Christmas just before Christmas on on g-protein couple receptors and Lefkowitz and kobilka are topping and tailing the program with the two keynotes so I'll get to meet them again yeah absolutely now what did actually the two Nobel Prize winners do the Nobel Prize gets awarded in December these guys might not get to your conference I think they should do I can't member the date of the Nobel Prize ceremony is the conference's first week in December in Melbourne at Monash University what they did was to work out this structure by very careful experimentation isolating these receptors from the cells and then using x-ray crystallography to work out the structure almost in atomic detail so it sounds to me like these guys have given you the ultimate blueprint of the keyhole so all you guys around the world can now make all the keys absolutely and from this early work there are now quite a number of papers that have come out that have reported other g-protein couple receptors crystal structures which is extraordinary that we can now understand how these receptors work which are just a small part of each cell two level of almost the individual atoms and of course once you know the structures then you can start designing even more specific and better drugs so there are millions and millions of people worldwide that suffer with asthma it's a debilitating disease where that particular disease manifests itself in their inability to breathe easily they have constriction of the the tubes in their lungs and they find it very difficult to breathe one of the drugs is used to combat that is a agonist molecule a molecule stimulates one of these g-protein coupled receptors this is the beta audrina scepter that resides within the bronchioles or the tubes of the lungs and what you'll notice that often a patient that has asthma if they're having an asthma attack will pull out their classic blue inhaler and take a puff and that puff delivers a effectively a molecule that mimics adrenalin binds to the beecher adrene acceptors in the lungs and the effect of that ligand binding to the betrayed receptor in the lungs is to open the lungs relax the tube so they open up so the air can pass more easily into the lungs and the patient can breathe again that's just one particular disease state there are a whole myriad of diseases where g-protein coupled receptor modulation by drugs allows people to live normal lives I think it's a really well deserved prize and I don't think anybody could grab such a wonderful piece of work being rewarded with this prize in my pocket I've got this and this is a real Nobel Prize medal capstone exercise excel 2018 page 445 Marist Brothers.

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