Perspective on chemistry and biology

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Perspective on chemistry and biology
Sarah O'Connor in discussion with Dirk Trauner
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Prof. Sarah O’Connor talks about chemical biology, alkaloid biosynthesis, and her career path. The questions were prepared and asked by Prof. Dirk Trauner.
Keywords reactions biology
Angelic acid
Sense District Organische Chemie
Elektrolytische Dissoziation Chemical plant Chemistry
Setzen <Verfahrenstechnik> Cell fusion Chemical plant Food
Cell growth Process (computing)
Systemic therapy Reaction mechanism Fiscal year Sea level Wine tasting descriptors Process (computing)
Octane rating Biotechnology River source
Area Weinfehler Blue cheese
Area Volumetric flow rate
Anomalie <Medizin> Azo coupling
Phase (waves)
Area Organische Chemie Functional group
Organische Chemie
Systemic therapy Sea level
Infrastructure Sea level
Infrastructure Chemistry Hope, Arkansas
Metabolite Chemical plant Medical history Chemistry
Naturstoff Phase (waves) Metabolism Chemical plant Biotechnology Hope, Arkansas
Alkaloid Naturstoff Biosynthesis Transcription (genetics) Zunderbeständigkeit Genome Chemistry
Metabolism Chemical plant Electronic cigarette Process (computing)
Drop (liquid) Chemical plant Multiprotein complex Chemistry
Setzen <Verfahrenstechnik> Naturstoff Metabolic pathway Azo coupling Metabolism Soil Biotechnology Genome Biochemistry
Naturstoff Systemic therapy Chromosome Metabolic pathway Chemical plant Genome Hope, Arkansas Process (computing)
Synthetic oil Metabolic pathway Chemical plant Genome
Chromosome Organische Chemie Metabolic pathway Chemical plant Gene Genome Wursthülle
Anomalie <Medizin> Synthetic oil Metabolic pathway Functional group Transcription (genetics) Gene expression Metabolism Chemical plant Action potential Coke (fuel) Sea level Gene
Sense District Wursthülle Periodate
Alkaloid Gene product Sense District Molecule Functional group Chemical plant Chemical structure Gene Hope, Arkansas Chemistry
Enzyme Walking Gene Chemical reaction Chemistry
Ageing Functional group Chemical property Motion (physics) Chemistry
Alkaloid Naturstoff Activity (UML) Mass spectrometry
Alkaloid Systemic therapy Artificial leather Chemical property Morphine Opium
Chemical plant Morphine Sea level
Potenz <Homöopathie> Plant breeding Stereoselectivity
Grading (tumors) Stickstoffatom
Molecule Metabolism Chemical plant Photosynthesis
Alkaloid Functional group Chemical plant Electronic cigarette
Alkaloid Chemical plant
Functional group Pathogenicity Chemical compound Chemical plant Resistenz Hope, Arkansas
Process (computing)
Reactivity (chemistry) Molecular biology Biosynthesis Organische Chemie Wursthülle Chemistry
Grading (tumors) Organische Chemie Tool steel Sea level
Emission spectrum Biosynthesis Organische Chemie Alkalinity Transformation <Genetik> Elektronentransfer
Neoteny Functional group Action potential Ausgangsgestein Genome Pharmacy Falconry
Synthetic oil Organische Chemie Infrastructure Transformation <Genetik>
the aide said it's great to hear you.
it made me move because you can read you went from york city to the angeles from the waist calls for these calls them from these calls to europe uk that is that our heart and wondering what it was like for you with his last who would like to have differences that is are beyond even the e.u. on me file.
and may fall would be interesting than on while i did have to learn had the same he filed because i learned if you say apple during and on organic chemistry lecture people assume that you saying that all cyan developing a little bit of a british accent at least in that sense i would have to say by moved to the uk has been a very good one.
there for about a year and a half now and i'm very happy there my move was motivated because my research was moving a little bit away from chemistry and more towards plant biology so i felt that it was very important to make sure that i had at least some association or affiliation.
with a plant biology or some type of plants research institute and the john innes center is one of the best plant research centers in in the world involving to move more quickly through in the united food through good comparable with fusion well there are some great plant biology us centers and apartments in the united states.
it's odd and i did look at some of them but there was something attractive about trying living in europe off for job as a change and beautiful bible rewarded with yellow growth was so in a way it was from a personal and it was a little bit of an adventure to just try living in a completely replace.
so different to fight in terms of funding for its high so i was very worried about funding when i first took the position i'm actually right after i accepted the position to the united kingdom was talking about taking fiscal austerity measures and i was very worried and but i was very pleased.
just because the united kingdom made of a commitment to science research funding and of levels of funding for scientific research were held constant at at at have a good level. the funding the mechanics of the funding system are in many ways different from the united states i think fundamentally writing grants is always the same you need to have a good idea you need to have some preliminary data to back up that idea and you need loads of jobs of doing it from do gooder.
you get the moment the so that my major our one of my major sources of funding is b b s r c which is bio science and biotechnology research council it's essentially i would say the equivalent of the nih in the united states and across england it's there is about a twenty to twenty five percent success rate.
both on the little blue ridge abuse there is a loser's bars are very good news for his goals are yes at absolutely i will say that being in a more biologically based area has i think given me some advantages in terms of getting funding i think that those subject areas are at least right now.
somewhat favored on in in terms of some of the of the area's a priority that to our research council's on our are giving so i do think that it is difficult to get off funding for us and that occur again a chemistry on in the uk and also from what i know in the united states as well and the drums low flow student.
and so up to one thing which was the imperfect your or your research programs is that you know the review three are a few life for my guess is opposed of ohio it say that ph d. student ship is the most different of of the academic the differences between the uk and the united states arm is.
so i will say that the b.s.e. is now funding of variety of student ships and those students ships now last four years not three years which i think is from my perspective of much more reasonable length of time for ph d. i don't know whether the ph d. students necessarily agree with that but i think that for years as an appropriate like the time for a ph d..
with over five years pros a little bit too long ago think feet of won't do that you'll get get i think i'm in four years you can really expect a student particularly one who has experience from a master's degree to get up to speed and to publish a couple of very nice papers think they work work hard enough.
the project is planned carefully and so i it i in some ways missed the freedom of having a ph d. student come in and we have the luxury of time in which we can just sort of have to figure out a project over the course of a year or so that we don't really have that luxury.
you'll both was wondering experimental phase yes exactly exactly nokia could be a mere in europe and in in the uk are you most of note is that women overall fully under a prison to at least with respect to some fifty go again a chemistry in take a little that's an interesting question and i completely agree with that.
observation and i have thought about this observation many times over the last fifteen years and i don't have a great explanation for it going to be much worse in europe the united states one thought that i have is that.
the more women you have an area are the low less or the more inclined young women will be inclined to follow so i do think in the united states there is a vibrant community or a vibrant group of women in organic chemistry and since.
that organic chemistry and i think just their presence in the community and their leadership in the community are undoubtedly inspires younger women to to fall in their footsteps.
it is so i think that in in a way you just kind of need to get the ball rolling and you need to get a critical mass and other programs the euro which might go play yeah so one thing that are really impressed me about the university system in the united kingdom is they have a program called the athena swann award.
and this is a program that requires a university arm of war department it can be awarded of both the university and a departmental level to write up a comprehensive plan detail how they're going to.
the change the infrastructure to encourage women to have of of remain in on the of as faculty members and also to get promoted to the senior ranks of faculty levels and i think that's great i think that shows real commitment to go off on the part of the use of the uk universities.
system and that being said i think it's also really critical to note that no matter how much infrastructure and how many programs to generate it really everything is really depended on the individual people involved so you absolutely need support of and forward thinking senior faculty members in chemistry apartments any kind of.
and to really promote arm of the the the advancement of of when science both though it's talk about our convoy it's richer as your mother of your heart those who only also revealed that my hope and the larger unit good as you know all of the development of his department is closely intertwined with local it came.
history of thinking back to reach that could be learned that the like i always consider the beginning of world of modern or rational again uk mr a more layers so driven by a article it came as a manager for chemistry i wonder what you take is on the future of this field in the future of plant metabolites or how they're going to carry.
the organic a ministry a fork and for the next phase of development art my hope is that plants are metabolism plant natural product by a census is entering a renaissance and i think that this renaissance is being driven by advances in the biotechnology steered namely the incredible.
you are d.n.a. sequencing our methodology these techniques that are now out there that enable us to gather and interpret incredibly large swaths of genomic and transcript omnicom information really on an individual laboratory scale so quickly and in a relatively inexpensive car.
last and i think having access to that genetic material and being able to interpret it is going to be a is going to enable us to correlate the biology of natural product and alkaloid by a synthesis with the chemistry so what does this compare to hire and involves slow or cool a microbe for that matter well i.
would say that it's looking a plant metabolism is a much slower process and looking at microbial metabolism and and in fact i think if you look through the literature you can see that really the the organic campus i think if the high end.
weird of plants chemistry really in the fifty's sixty's seventy's and and all the way up into the eighty's and i think you notice a drop off in the literature starting in the late eighty's early ninety's because that's when d.n.a. sequencing technology started to come online and it really wasn't a playable to the complexity of plants at that stage so most.
people really switched over to microbes at that stage and started applying all of these new of biotechnology and biochemical techniques to microbes and i think that's why we've had such tremendous advances in microbial metabolism for example arm so we can now get a genome.
for us soil bacterium for example in a couple of days and there are incredible algorithms and methods to go and quickly scanned those genomes and really pick out the bile synthetic pathways that increase in codes a very complicated natural products very very quickly and that type of methodology.
he is not yet there for plants arm but we are currently working on it and it's its it's my hope that even though i suspect that it will always be a slower process for plants we we will get their of for for even the most complex of plant plant systems in terms of being able to the convoluted use these amazing natural product pathways.
quickly as deserve all the old improve what is your view need you are ruthless was a lier use a defective to deal with multiple chromosomes abroad were more hours of the world also planned genomes are big some of them are very big some of them are bigger than human genomes which upset some people i think people like to think that we're the most complicated work.
cousins on the planet of but at least imagine gnomic perspective that is not correct so it's sheer quantity of genomic information that you have to deal with the many plant by of synthetic pathways aren't.
of organized very nicely on the chromosome as microbial pathways or microbial pathways tend to be organised to stop or ons so it's.
an incredibly convenient way to be able to scan a genome of a microbial organism and really have all of the genes arrange sequentially next to one another on on the chromosome and that is frequently not the case with plants so each gene really has to be found individually and so i think the methodology that is.
as i think really proving to be the breakthrough in cracking plant metabolism is not so much using genomic information but using transcript information so you actually look at the genes that are being expressed and you look at the levels that which those genes of being expressed and if you profile. while those expression levels over a whole variety of different tissues you can start to use software to observe the patterns among various different expression levels and there is a technique called coke special analysis where we can say ok are we know one of the bias and that of genes in the pathway and. we're going to make the assumption that the other genes in the bias and that path we're going to have similar expression profiles and so we can use the software to really. i have the the the expression profile day to tell us that and so we can win no down from save thirty seven thousand genes that might be are expressed in a in a transcript all too much more manageable number of potential buyers synthetic gene candidates and then assess the function of those gene candidates by a group was you'd be real be able to.
to predict for better products are colloidal implants were and elucidate the as we can do is what makes them in that period are under i like to hope that's going to be the case but it is going to be a much much harder problem because in a sense with microbes they really have of the the way that the.
biology works is that the all of the answers are given to us in the sense of we have a gene koster that really has all of the pieces in place so is the hope is with with microbes in this this is this is very often true you can look at all those pieces and put together a hypothesis based on the structure of the molecule and the proposed function of those.
of of those in code gene products but if you don't have a finite set of genes to to look at the prospect of novo prediction becomes a little bit harder so my personal feeling is that with plant chemistry specially plant alkaloid chemistry.
we're always going to be dependent on our chemical knowledge or chemical intuition. biomimetic reactions of of chemical reactive the to really be able to put together a reasonable chemical hypotheses and then find the genes and the corresponding enzymes are that that could potentially carry out those steps but what we broke a typical techniques other trays aka lloyds sir richard's super by.
eric do for my birthday after a motion is that our clothes occur in vast quantities of the would like to pick your brain way and this is a lot of the legislation's of our good chemistry but also i wonder whether there are hundreds of for a minor article it to the age group the places which could have fascinating structural and biological properties i think that's.
it's absolutely true i think that with the mask a tram a tree our technology that's coming on to line and again that's becoming much more accessible to the individual investigator who can may not be an expert mass spectrometry but who might be an expert in natural product by us and this is who can utilize this this technology. we are in their own lab yes i think we will absolutely be able to find arm more and more unusual alkaloids that are produced in trace quantities whether or not they'll have super biological activities arm of i think it's reasonable to speculate that they might have interesting interesting.
properties high don't know that out the woods by a larger produced in huge quantities i know that morphine is one of your favorite alkaloids and morphine is produced in huge quantities by opium poppy by the a listers or other prizes grow she was it's an artificial system so opium poppy.
he has been selectively bred for morphing content for three thousand years arm so that i think the production levels of morphine and i think more thing constitutes something like twenty percent of the plant latex which is incredible.
the amount that really highlights the power of selective breeding being able to preserve go for example corn into three logic or do with him or schilling whatever the illusion would reduce get real you should live optimize corner maybe old greeks know i also think there's builds a lot of wrote another that's true there.
is there are some examples of her project shows that robotics existed relied on this and the i remember when i was a great student direction and the grades you there was thought the article is a mate but plans to the polls of nitrogen which i found the completely silly and the very and economical idea or.
and i was wondering what your pick of this as well i think first you have to consider that plant metabolism its is somewhat different than say animal metabolism and it's been told me that given our the plants ability to utilize photosynthesis.
the plant does have energy to expand a.t.p. for example to expand in synthesizing some of these complex molecules without really very much on evolutionary expense of two to two itself arm was devoted to improve remain under way for the decision to allow.
so whether those that's ok with a different different question.
but i guess i'm really to answer your question you need to know what the and dodges function of these alkaloids are so why is the plant making them in the first place and then i think you can rationally asked the question why does the plant make so much of the end we know very little about why certain many.
most alkaloids are made by various plants something of interest you and your is what it is and that's again another reason why i was interested in moving to a place that did more plant biology because of this is a question that we would need some help and expertise in trying to address and i won't say that we have any answers yet.
but we are looking at the ability of some of the article is that we're interested in to enable the plant to resist infection by certain pathogens arm and dumb.
i hope that that will tell us something about potentially why some of these are clothes are made and maybe even from a practical standpoint of provide some new and interesting compounds to help plants are resist some of these a result some of these pathogens and feel i'm sure of her book is we all are your of because your group room.
old launches that the figure would take slow the law has a degree that i was wondering what your pick abuses would you rather old ways his films that over a big risk the questioning or over new technology to go.
but the of any way or the secret recipe i know i had bullet we would like to hear i have no secret rest day there's no magic bullet i first and foremost i think you should do whatever you find most interesting and exciting i don't think that you should be doing scientific research an usher absolutely.
and crawled by the questions that you're asking so that's i think that's the most important thing for him i certainly think that it's the important for a person just starting out it's really your job to drive the field forward so you need to be thinking about.
the ways in which you can do things a little bit differently and so i think in an ideal scenario you take what you learned as a ph d. student and what you learned as a poster and try to combine them in a new and novel way and start your independent career doing something of a little bit differently tom so in.
my own case i did buy organic chemistry as a ph d. student and i think really have picked up the skills of organic synthesis and thinking about chemical reactive he thinking about analytical chemistry and then as a post-op i learned about and somalia g. molecular biology.
and some of the basic tools are really thinking about how to manipulate organisms that at the at the genetic level you feel because the little boy was killed that from grade school though during or both of you as you know it's amazing i i feel really great when i have a post-op come up to me with the t.l.c. and explain it to me or.
many more spectrum and i can say up you've got the aisle to hide because i can see the the the peak at nine p.m. so i think actually that of training in our organic chemistry has really put me at an advantage in looking at the biology of plan alkalinity.
capitalism because we can really combined organic synthesis and the state of the art of transfer filmic sequencing plan transformation techniques to really i think do something that's that state of the art arm by combining those those to do.
disciplines and i would if i would advise young people to really think about that how you can bring to seemingly disparate disciplines together and and i i think of this the potential for some really fundamental questions are being answered in new ways by doing that you're looking for a girl your group you're going to grow.
the reviews it wasn't for the chemist to pick up genomics so the rycroft out of his youth who buy own from up expired the molecular planning or your parents live her hair found by companies anyways a more work to examine these there is a day yes i do but i think that's partly because i'm fortunate to have very smart post docs.
but i can tell you that i have a post-op he was trained as a synthetic organic chemist in tom organic the talent methodology and he is right now doing plan transformation and i think provided that you're in an environment where you have the infrastructure and you have the expertise namely.
people to help show you how to do with the correct way it's it's absolutely possible great thing for much for thank you very much her.