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[Music]

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I'm David I'm a prebiotic chemist

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really more of an organic chemist and in

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Becky's introduction talk she reviewed

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chemical structures to you so I hope you

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uh I hope you got that because it's

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otherwise it's gonna be a little rough

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ride but here we go alright so

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fundamentally life is a chemical

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phenomenon I don't mean to be

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patronizing with this I just want to

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highlight that you know you can see a

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schematic of DNA but it really does have

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fine chemical structure and that fine

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chemical structure is important for

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elucidating the origin of life so you

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know in experiments like the miller-urey

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experiment which we're all familiar with

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typically the thing that you find are

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amino acids so for example the you know

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the constituents of a protein but if

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what we're trying to figure out is how

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another class of biomolecules the

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nucleic acids came into existence the

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monomers of nucleic acids are

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comparatively more complex so compare an

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isolated amino acid to an isolated

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nucleotide and clearly the nucleotide is

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larger and more difficult to assemble

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the prebiotic we plausible manner so

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before I jump right into my chemistry I

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wanted to give you a little bit of an

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overview of how biology works today

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because that's how we are informed of

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what molecules to target in our

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prebiotic synthesis so DNA another

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schematic DNA is the hereditary molecule

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of all life with the exception of some

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viruses DNA is transcribed by a protein

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into an RNA message and then that RNA is

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translated by an enzyme called the

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ribosome which emphatically is not

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protein based it's RNA based and that

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gives you proteins but you require

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proteins in order for DNA to replicate

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itself so because of this we have a

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chicken and egg problem right we need

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proteins for DNA and we need DNA to code

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for protein so how do we get out of that

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cycle well there's there's a clue here

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in the central dogma of molecular

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biology

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which is RNA RNA in the central dogma

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fills two different roles one of them is

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informational in the form of messenger

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RNA and the other one is catalytic in

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the form of the ribosome which itself is

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a ribozyme of an RNA enzyme so since RNA

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has the capability to perform both these

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functions which today are mostly

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partitioned between DNA and protein it's

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thought that RNA played a really

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critical role at or close to the origin

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of life all right so that leads to this

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popular idea called the RNA world

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hypothesis which is but before I get

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into that I want to explain to you

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exactly what RNA is and how its distinct

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from DNA so here's that schematic again

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and here's the fine structure again RNA

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is very similar so if you look at DNA

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you have this phosphate deoxyribose

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backbone with the nucleobases here RNA

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is similar but there are just a few

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modifications so in DNA we have the

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nucleobases I mean and in RNA we have

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the perhaps more perhaps simpler

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nucleobase uracil which pairs with

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adenine DNA has a hydrogen atom here

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where RNA has a hydroxyl group now

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superficially that might seem to make

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RNA more complicated but actually that

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hydroxyl group is easier to produce in a

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prebiotic ly plausible manner than the

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deoxyribose of DNA and that those small

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modifications have profound consequences

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in what RNA and DNA are able to do so

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DNA is optimized for information storage

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and transfer RNA can perform that

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function too but because of this

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hydroxyl group there is a change in the

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bulk structure of RNA which allows it to

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more readily access catalytically active

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structures all right so now we're at the

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RNA world hypothesis which is the idea

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that before the DNA protein based

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biochemistry of today we had a

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biochemistry that was predominantly

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based on RNA I just want to really

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quickly note that there that idea as

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I've just stated it has been contested

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of it lately but let's just stay within

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that paradigm

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for now and I'm gonna give you a

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historical perspective on how it's been

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investigated so what we want to get to

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is this polymer RNA the traditional

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approach has been to start from simple

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prebiotic precursors sorry there's a

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little bit of feedback historical

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approach has been to start from simple

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prebiotic precursors and build your way

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up to the polymer now if you draw it

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like this it looks pretty reasonable

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right and this is maybe you've heard of

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the term paper chemistry it's it's you

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can draw it on paper and it looks really

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pretty but it's completely wrought with

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issues so for example if we want to get

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the sugar ribose exclusively that's a

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big problem because the chemical

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reaction that's typically invoked in

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order to produce sugars in a prebiotic

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we plausible manner is totally non

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selective and produces a variety of

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sugars but even if we could produce

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ribose exclusively we have a further

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problem in that the canonical

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nucleobases AUG and c do not react with

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ribose in water in the absence of

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enzymes the form nucleosides

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even if we could form nucleosides though

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there are difficulties in

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phosphorylation and i'm sure some of you

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are aware of attempts to overcome these

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difficulties which indeed do

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phosphorylate organic compounds but

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there remains the problem of

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polymerizing those organophosphates to

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get this phosphodiester polymer so we in

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the HUD lab and in the Center for

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chemical evolution in general have this

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new approach which is basically the

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structures that are present in life

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today are not necessarily those that

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were present at the very origin of life

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and that applies to RNA as well so if

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you're willing to accept the idea that

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DNA is the descendant of RNA perhaps RNA

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is the evolutionary descendant of a

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series of pre rnas going all the way

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back to this proto-aryan a it's an older

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so what we do is we take the nucleic

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acids of today and we partition them

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into three structural components so one

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of them is the ionized linker which

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today is phosphate one of them is the

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tri functional connector which today is

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either ribose in RNA or deoxyribose in

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DNA and then we have the recognition

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units which are the canonical

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nucleobases AUG NC and these structural

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components we think would still be

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present in the most ancient nucleic

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acids but they might have been replaced

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with different chemical moieties which

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had chemical properties more amenable to

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spontaneous formation than this

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phosphodiester polymer okay so first I'm

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gonna focus on the recognition units of

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RNA and how we can start to speculate on

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what if what may have preceded the

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excellent nucleobases so if you have a

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prebiotic ly reasonable milieu of

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nucleobases some of them will be the

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ones that are present in life today but

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surely just out of the natural

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trajectory of prebiotic chemistry you're

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going to have a bunch of other

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heterocycles that are not featured in

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life today

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so how do we sort out from that complex

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mixture a set of nucleobases that can

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form an informational system well let's

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use the concept of super molecular

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assembly to our advantage

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some of these heterocycles with will

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have the ability to spontaneously self

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sort into a super molecular aggregate

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and they'll exclude all the other

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nucleobases once we had that non

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covalent super molecular assembly

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perhaps we can use that as a scaffold to

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create a covalent polymer so these are

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the heterocycles that were most

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concerned with they have the ability to

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form these super molecular structures by

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having two hydrogen bonding phases so

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what that means is that they have these

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edges that have very polar sides and

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they snap together with their pairing

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partners to form these hex-head

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structures so the bases that we're

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concerned with are barbaric acid try me

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know permitting or tap as I'm going to

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refer to it in the rest of the talk

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cyanuric acid and Melanie they all have

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the ability to form this hex ad which

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forms spontaneously and water the really

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cool thing about this hex ad is that

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once it's formed it presents a very

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large hydro flow

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like surface and water and that is very

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unfavorable to present to bulk water so

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what it does is stack one on top of the

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other in order to hide those hydrophobic

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faces and you have this super molecular

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assembly as a result all right so we

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have these non-canonical nuclear bases

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that we want to form polymers out of do

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they actually react with ribose in order

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to form nucleotides turns out that they

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do this is work from 2013 from Michael

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Chen and Brian Cafferty in the HUD lab

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so if you take this hetero cycle tap and

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react it with ribose there are a variety

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of products that you can form and the

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details of this are not important

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besides that the one you form in the

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greatest yield is the beta rival for

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your an aside which what that really

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means is it has the same conformation

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that nucleus sides in life today have so

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the problem is that if you had ribose

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there were all these possibilities and

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it's not immediately clear why we have

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this one in life today

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but this suggests that it's just the

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natural outcome of the chemical reaction

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and if you take this nucleus side which

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we call tark and you incubate it with

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cyanuric acid in the appropriate buffer

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you get these super molecular assemblies

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and you can even visualize them by

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atomic force microscopy you can see here

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that they have the appropriate diameter

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for what we predict this super molecular

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assembly to be all right so that's cool

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but if you want to have an informational

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system you need to have at least two

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units so just having tap is not enough

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so what we're gonna do is take

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inspiration again from excellent biology

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and make inferences about what extinct

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biology could have been like so we have

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the au base pair which cannot form

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spontaneously in a prebiotic we

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plausible men or remember that but

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perhaps we can have a similar base pair

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which is structurally analogous but that

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can form spontaneously improve on acquis

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plausible manner just like tark and it

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turns out that that is indeed the case

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so barbaric acid and melamine both have

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the ability to react with ribose in

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water ribose 5-phosphate in this case to

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form nucleotides and they have the

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ability to assemble just like before

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at the appropriate pH to form the super

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molecular assembly and again you can see

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this by atomic force microscopy and

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another really cool feature of the

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system is that

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these fibers are so long and so

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interlinked that they prevent the bulk

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flow of water so you get this hydrogel

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00:11:07,790 --> 00:11:05,819
so that's a cool material property but

278
00:11:10,040 --> 00:11:07,800
what's really important here that I want

279
00:11:12,259 --> 00:11:10,050
you to take away is that we have an

280
00:11:13,550 --> 00:11:12,269
information system now as long as we can

281
00:11:16,100 --> 00:11:13,560
figure out a way to polymerize them

282
00:11:18,980 --> 00:11:16,110
because we have two units so really

283
00:11:21,110 --> 00:11:18,990
quickly I want to tell you about another

284
00:11:23,090 --> 00:11:21,120
component of RNA which is the tri

285
00:11:25,519 --> 00:11:23,100
functional connector so just now I was

286
00:11:27,829 --> 00:11:25,529
telling you about how we're not going to

287
00:11:29,569 --> 00:11:27,839
deal with the canonical nucleobases

288
00:11:30,980 --> 00:11:29,579
because they don't react with ribose in

289
00:11:32,840 --> 00:11:30,990
water but if we're willing to accept

290
00:11:34,550 --> 00:11:32,850
that the nucleobases may have been

291
00:11:36,230 --> 00:11:34,560
different we should have that exact same

292
00:11:38,210 --> 00:11:36,240
attitude with all the other components

293
00:11:39,499 --> 00:11:38,220
of RNA so for example we're going to

294
00:11:41,720 --> 00:11:39,509
take the tri functional connector which

295
00:11:44,090 --> 00:11:41,730
today is ribose and see if it could have

296
00:11:45,530 --> 00:11:44,100
been something different now I mentioned

297
00:11:47,780 --> 00:11:45,540
before that it's really difficult to get

298
00:11:49,280 --> 00:11:47,790
ribose in a selective manner because the

299
00:11:51,110 --> 00:11:49,290
reaction that typically is invoked to

300
00:11:52,819 --> 00:11:51,120
produce sugars the foremost reaction is

301
00:11:54,769 --> 00:11:52,829
inherently not selective it produces a

302
00:11:56,210 --> 00:11:54,779
ton of sugar it's like there's a

303
00:11:57,740 --> 00:11:56,220
chromatogram that was shown in Becky's

304
00:11:58,850 --> 00:11:57,750
slides I think that shows the products

305
00:12:00,319 --> 00:11:58,860
of the foremost reaction and you know

306
00:12:02,900 --> 00:12:00,329
there's like a hundred Peaks there's

307
00:12:05,929 --> 00:12:02,910
even more than that so we had this

308
00:12:07,429 --> 00:12:05,939
question if you do naturally produce a

309
00:12:10,100 --> 00:12:07,439
ton of sugars in these prebiotic

310
00:12:12,439 --> 00:12:10,110
reactions can a non-canonical nucleobase

311
00:12:14,329 --> 00:12:12,449
react not just with ribose but perhaps a

312
00:12:16,400 --> 00:12:14,339
suite of them to form

313
00:12:19,579 --> 00:12:16,410
non-canonical nucleosides or glycosides

314
00:12:21,980 --> 00:12:19,589
really now again chemical structure is

315
00:12:23,540 --> 00:12:21,990
terrifying but all I want you to take

316
00:12:25,189 --> 00:12:23,550
away from this is that there's a variety

317
00:12:27,170 --> 00:12:25,199
of sugars which ostensibly have

318
00:12:29,449 --> 00:12:27,180
different chemical properties and may or

319
00:12:31,059 --> 00:12:29,459
may not react with tap so what I'm gonna

320
00:12:36,230 --> 00:12:31,069
do is I'm gonna take a general sugar

321
00:12:37,850 --> 00:12:36,240
just read this word and react it with

322
00:12:41,240 --> 00:12:37,860
tap and you can get a bunch of different

323
00:12:44,660 --> 00:12:41,250
products and it turns out that it works

324
00:12:46,850 --> 00:12:44,670
so in this chart I have the yields here

325
00:12:49,429 --> 00:12:46,860
so we did this either at pH 1 or pH 7

326
00:12:51,350 --> 00:12:49,439
because it turns out that this reaction

327
00:12:53,150 --> 00:12:51,360
happens to be acid catalyzed but I want

328
00:12:54,829 --> 00:12:53,160
you to note that on every single

329
00:12:56,720 --> 00:12:54,839
structure here the reaction worked and

330
00:12:58,329 --> 00:12:56,730
at least one of those conditions every

331
00:13:02,389 --> 00:12:58,339
single one and that's important because

332
00:13:04,670 --> 00:13:02,399
it's often just assumed without any kind

333
00:13:06,410 --> 00:13:04,680
of you know it's assumed a priori that

334
00:13:07,850 --> 00:13:06,420
ribose was first because that's what's

335
00:13:09,769 --> 00:13:07,860
in biology today but that's not

336
00:13:10,079 --> 00:13:09,779
necessarily a good assumption because at

337
00:13:11,910 --> 00:13:10,089
least

338
00:13:14,220 --> 00:13:11,920
from a reactivity standpoint there's

339
00:13:16,079 --> 00:13:14,230
nothing special about ribose all of

340
00:13:17,340 --> 00:13:16,089
these sugars all of them have the

341
00:13:22,259 --> 00:13:17,350
ability to react with the non-canonical

342
00:13:23,400 --> 00:13:22,269
nuclear base okay great so now this is

343
00:13:26,280 --> 00:13:23,410
gonna really be for the chemists in the

344
00:13:28,439 --> 00:13:26,290
room we wanted to take a closer look at

345
00:13:30,720 --> 00:13:28,449
the structural outcome of some of these

346
00:13:32,579 --> 00:13:30,730
reactions now it turns out that glucose

347
00:13:33,569 --> 00:13:32,589
is one of the easiest sugars to study

348
00:13:40,470 --> 00:13:33,579
because it's one of the most well

349
00:13:42,239 --> 00:13:40,480
behaved and structurally congruent so if

350
00:13:43,679 --> 00:13:42,249
we take a glucose derivative and react

351
00:13:46,829 --> 00:13:43,689
it with tap there's basically six

352
00:13:48,660 --> 00:13:46,839
possibilities up here these all have the

353
00:13:50,519 --> 00:13:48,670
tap nucleobase pointing up

354
00:13:52,439 --> 00:13:50,529
that's called beta these all have the

355
00:13:54,389 --> 00:13:52,449
tab nucleobase pointing down that's

356
00:13:56,369 --> 00:13:54,399
called alpha the reason that's important

357
00:13:59,819 --> 00:13:56,379
is because in life today almost all

358
00:14:02,910 --> 00:13:59,829
glycosides of you know of nucleobases

359
00:14:05,040 --> 00:14:02,920
are beta and it turns out the one we get

360
00:14:08,040 --> 00:14:05,050
when we react tap with glucose or

361
00:14:09,809 --> 00:14:08,050
glucose derivative all of the products

362
00:14:11,519 --> 00:14:09,819
are beta so that's very interesting but

363
00:14:14,610 --> 00:14:11,529
that might be intrinsic to glucose

364
00:14:17,069 --> 00:14:14,620
derivatives nevertheless when you get

365
00:14:18,929 --> 00:14:17,079
the reaction of tap with glucose you get

366
00:14:22,019 --> 00:14:18,939
every possible substitution on the tap

367
00:14:24,239 --> 00:14:22,029
molecule because tap turns out to be a

368
00:14:26,449 --> 00:14:24,249
multi dentate nucleophile so you can

369
00:14:28,980 --> 00:14:26,459
have different positions of substitution

370
00:14:30,989 --> 00:14:28,990
glucose 6-phosphate behaves the exact

371
00:14:33,179 --> 00:14:30,999
same way and strangely n acetyl

372
00:14:35,460 --> 00:14:33,189
glucosamine does not tolerate the c

373
00:14:36,840 --> 00:14:35,470
substitution this is a really esoteric

374
00:14:39,569 --> 00:14:36,850
point but that might have to do with

375
00:14:42,290 --> 00:14:39,579
diminished electro felicity of the

376
00:14:45,569 --> 00:14:42,300
relevant intermediate in the reaction

377
00:14:47,809 --> 00:14:45,579
okay so super molecular assembly again

378
00:14:49,980 --> 00:14:47,819
is it possible that these non canonical

379
00:14:51,749 --> 00:14:49,990
nucleus sites which do not feature

380
00:14:52,259 --> 00:14:51,759
ribose have the ability to assemble in

381
00:14:54,509 --> 00:14:52,269
water

382
00:14:56,610 --> 00:14:54,519
well I took one of them and I purified

383
00:14:58,949 --> 00:14:56,620
it just because it's easier to study

384
00:15:00,900 --> 00:14:58,959
that way when you incubate it with

385
00:15:02,280 --> 00:15:00,910
cyanuric acid at the appropriate pH it

386
00:15:04,710 --> 00:15:02,290
forms assemblies but they're really

387
00:15:08,040 --> 00:15:04,720
small this is again an atomic force

388
00:15:10,110 --> 00:15:08,050
microscopy image that's weird but what

389
00:15:11,759 --> 00:15:10,120
if I take the crude reaction mixture so

390
00:15:14,189 --> 00:15:11,769
what that means is I perform a reaction

391
00:15:15,569 --> 00:15:14,199
and I took the reaction without any

392
00:15:18,449 --> 00:15:15,579
purification and mixed it with cyanuric

393
00:15:20,160 --> 00:15:18,459
acid those form very long fibers which

394
00:15:23,069 --> 00:15:20,170
is interesting because this is the more

395
00:15:23,940 --> 00:15:23,079
prebiotic lee reminiscent scenario so

396
00:15:26,160 --> 00:15:23,950
maybe that's telling

397
00:15:28,860 --> 00:15:26,170
something about how these polymers got

398
00:15:30,750 --> 00:15:28,870
going okay really quickly I just wanted

399
00:15:32,070 --> 00:15:30,760
to point out that in this study we had

400
00:15:34,620 --> 00:15:32,080
an interesting result which is that a

401
00:15:36,660 --> 00:15:34,630
sugar called rib ulos we anticipated to

402
00:15:38,880 --> 00:15:36,670
react with tap in this manner to form

403
00:15:40,290 --> 00:15:38,890
these strange nucleus sides but it turns

404
00:15:41,970 --> 00:15:40,300
out that there's no evidence for their

405
00:15:44,550 --> 00:15:41,980
formation rather it forms these

406
00:15:46,680 --> 00:15:44,560
arabinose IDEs and dry besides that's

407
00:15:47,640 --> 00:15:46,690
cool because Ryba sides are nucleus

408
00:15:50,190 --> 00:15:47,650
sites those are the things that are

409
00:15:52,050 --> 00:15:50,200
present in life today now why are we

410
00:15:53,190 --> 00:15:52,060
excited about this I told you earlier

411
00:15:55,050 --> 00:15:53,200
that it's really difficult to get to

412
00:15:56,790 --> 00:15:55,060
ribose in a prebiotic ly possible manner

413
00:15:58,710 --> 00:15:56,800
but it turns out that rib ulos is a

414
00:16:00,540 --> 00:15:58,720
little bit easier there's a synthesis by

415
00:16:03,360 --> 00:16:00,550
ROM Christian Murphy where you can get

416
00:16:05,670 --> 00:16:03,370
to Regulus and in our system we think

417
00:16:08,640 --> 00:16:05,680
what's going on is that it's isomerizing

418
00:16:10,200 --> 00:16:08,650
in situ to ribose and arabinose and then

419
00:16:12,180 --> 00:16:10,210
reacting with tap to form these

420
00:16:14,370 --> 00:16:12,190
nucleotides so that's pretty cool this

421
00:16:16,530 --> 00:16:14,380
is the proposed prebiotic synthesis of

422
00:16:19,470 --> 00:16:16,540
rib EULA's and if you want to learn more

423
00:16:24,570 --> 00:16:19,480
please see Tyler's poster which is all

424
00:16:27,060 --> 00:16:24,580
about this okay so just to recap we are

425
00:16:28,350 --> 00:16:27,070
taking the stance that the structures

426
00:16:29,760 --> 00:16:28,360
that are present in life today are not

427
00:16:31,680 --> 00:16:29,770
necessarily those that were present at

428
00:16:35,100 --> 00:16:31,690
the origin of life and most importantly

429
00:16:36,780 --> 00:16:35,110
RNA was not emphatically first so if we

430
00:16:38,970 --> 00:16:36,790
take this approach we get some really

431
00:16:41,370 --> 00:16:38,980
interesting results the nucleobases

432
00:16:42,420 --> 00:16:41,380
could have been different we go to ones

433
00:16:44,250 --> 00:16:42,430
that are more reactive and have a

434
00:16:45,630 --> 00:16:44,260
greater propensity for self-assembly the

435
00:16:49,430 --> 00:16:45,640
sugars could have been different in that

436
00:16:51,480 --> 00:16:49,440
sorting that out is that's gonna be fine

437
00:16:52,920 --> 00:16:51,490
we didn't I didn't talk about the

438
00:16:55,080 --> 00:16:52,930
ionized linker but we are investigating

439
00:16:59,190 --> 00:16:55,090
that in our lab and if you want to learn

440
00:17:01,530 --> 00:16:59,200
more just ask me later okay

441
00:17:03,360 --> 00:17:01,540
so I just want to thank everyone who

442
00:17:05,400 --> 00:17:03,370
made this possible Brian Cafferty was my

443
00:17:06,510 --> 00:17:05,410
mentor when I first joined the lab Kim

444
00:17:07,980 --> 00:17:06,520
Clark did all the atomic force

445
00:17:09,569 --> 00:17:07,990
microscopy that you just saw

446
00:17:11,610 --> 00:17:09,579
Tyler's our new graduate student who's

447
00:17:13,290 --> 00:17:11,620
taking on all this rib you low stuff I

448
00:17:15,270 --> 00:17:13,300
was really lucky to have really talented

449
00:17:17,850 --> 00:17:15,280
undergraduates Catherine and Megan and

450
00:17:18,600 --> 00:17:17,860
really great mentors especially ipi

451
00:17:27,329 --> 00:17:18,610
nicholas hi

452
00:17:40,660 --> 00:17:29,289
all right we have time for a couple

453
00:17:49,850 --> 00:17:47,540
hi we talk in your walk with interaction

454
00:17:52,220 --> 00:17:49,860
with Daffy and barbecue rig acid do you

455
00:17:55,220 --> 00:17:52,230
think that the interaction between

456
00:17:58,220 --> 00:17:55,230
tavern barbecue rig acid and their

457
00:18:00,680 --> 00:17:58,230
ribose phosphate derivatives is that

458
00:18:02,540 --> 00:18:00,690
depending on their inherent chirality as

459
00:18:03,890 --> 00:18:02,550
well could be

460
00:18:05,630 --> 00:18:03,900
so you're talking about the chirality of

461
00:18:11,990 --> 00:18:05,640
those nucleotides has endowed by the

462
00:18:14,510 --> 00:18:12,000
sugar yeah okay it could but we perform

463
00:18:16,190 --> 00:18:14,520
this study with commercially supplied

464
00:18:18,200 --> 00:18:16,200
sugars so they are in fatica ly not

465
00:18:19,970 --> 00:18:18,210
receiving they're all in an tio cured so

466
00:18:23,300 --> 00:18:19,980
we have not investigated that yet but

467
00:18:30,560 --> 00:18:23,310
there is research in our lab which find

468
00:18:32,360 --> 00:18:30,570
me later I'll tell you about that would

469
00:18:34,430 --> 00:18:32,370
it be possible then or have you tried

470
00:18:37,340 --> 00:18:34,440
something like that in which a chiral

471
00:18:42,560 --> 00:18:37,350
the or one part of it resolves another

472
00:18:43,910 --> 00:18:42,570
which is its that someone else's work in

473
00:18:58,750 --> 00:18:43,920
my lab and I can totally tell you all

474
00:19:04,960 --> 00:19:02,500
my grater in general what glucosides

475
00:19:08,410 --> 00:19:04,970
also something chromatic linked to a

476
00:19:10,360 --> 00:19:08,420
sugar a very very common implants which

477
00:19:12,640 --> 00:19:10,370
are used for all type of signaling and

478
00:19:15,700 --> 00:19:12,650
regulation do you think that if before

479
00:19:18,520 --> 00:19:15,710
was just on RNA and DNA really need us

480
00:19:20,080 --> 00:19:18,530
in understanding for example ancient

481
00:19:22,510 --> 00:19:20,090
signaling pathways or action networks

482
00:19:24,220 --> 00:19:22,520
because this thing's they might look

483
00:19:34,260 --> 00:19:24,230
more similar to work like plants and

484
00:19:36,100 --> 00:19:34,270
bacteria nowadays yeah yeah yeah okay so

485
00:19:38,500 --> 00:19:36,110
related to what you're saying

486
00:19:40,690 --> 00:19:38,510
it's interesting to think about how so

487
00:19:42,850 --> 00:19:40,700
many cofactors in life are basically

488
00:19:46,750 --> 00:19:42,860
nucleotide it's like NADH and stuff like

489
00:19:48,910 --> 00:19:46,760
that I think that that might bear a clue

490
00:19:51,610 --> 00:19:48,920
as to the origin of nucleic acids but it

491
00:19:53,770 --> 00:19:51,620
you know also possibly the origin of a

492
00:19:56,620 --> 00:19:53,780
more rudimentary biological system in

493
00:19:58,960 --> 00:19:56,630
general but we can talk yeah that can go

494
00:19:59,670 --> 00:19:58,970
into many avenues so I'll just leave it

495
00:20:01,870 --> 00:19:59,680
at that

496
00:20:03,940 --> 00:20:01,880
alright so in the interest of time we're