Hello and welcome to my blog! My name is Caroline and I am a PhD student at the University of Sheffield. My research project focuses on Striga - a genus of parasitic plants that devastates harvests by infecting food crops. I am exploring the defence reactions that can make host plants more resistant against Striga. Due to my ongoing battles with anorexia, I haven't made as much progress as I would have liked but I am determined to finish the course.
This blog charts the ups and downs of life in the lab, plus my dreams to become a science communicator and forays into public engagement and science policy....all while trying to keep my mental and physical health intact. Along the way, I'll also be sharing new plant science stories, and profiles of some of the researchers who inspire me on this journey. So whether you have a fascination for plants, are curious about what science research involves, or just wonder what exactly I do all day, read on - I hope you find it entertaining!
Wednesday, 25 December 2013
Saturday, 7 December 2013
Firstly, the growth chambers have now been cleared out for their maintenance overhaul between December- January. The remaining potted maize plants were put to good use in the Annual Departmental "Christmas Lecture". Based on a Royal Society Lectutre, but for an audience of primary school children, the topic this year was "Eating Sunlight: How plants harvest energy from the sun". Although I wasn't able to help out in the end, apparently this was a resounding success, in both content and for squeezing 1,200 children into the Octoagon Building. If even one of them is inspired to become a plant scientist, it will have been worth it! This made me consider what made me first interested in science; ultimately, I think my interest was first touched by the David Attenborough TV series, especially "The Blue Planet" with the episode featuring the curious creatures that lived at the darkest depths of the oceans. This does sound like such a cliche though! Even my supervisor says that David Attenborogh was partly responsible for her becoming a biologist. At that stage, however, I wasn#t really considering the plants (when I thought that studying whale sharks was still a realistic career option and not a chance in a thousand). It took a week long plant-science summer school, hosted by the Gatsby Plants Charitable Foundation, to change my mind. Featuring highly stimulating lectures and practicals (letting young students loose with temperature probes and cameras is always a recipe for madness), gorgeous accommodation, wonderful food, too much frisbee playing... this basically "brainwashed" (albeit in a very agreeable way!) the attendees to devote themselves to a career in plant research. But how did I end up working with Parasitic Plants? My super visor was invited to give a talk at Durham University as part of the Departmental Seminar Series; a weekly lecture conducted by a visiting speaker, followed by questions and refreshments. Many people still remember it as the "best seminar of the year" and after describing her work, she was good enough to mention that she had a PhD available if any undergraduates were interested. Happy twist of fate!
Hundreds of bejewelled fir trees meanwhile, have sprung up everywhere but no one seems to be researching the cause of this phenomenen, as everyone is too concerned about Christmas approaching. Indeed, a veritable scrum of events seems to be jostling for inclusion before the end of term: the Departmental Christmas Seminar, The Animal and Plant Sciences Christmas Party, the Lab Christmas Meal...not to mention the various festivities that postgraduate students organise among themselves!
I hope you are all coping with the mad rush of festivities. I hope I can make it out to the end of this busy term!
Friday, 15 November 2013
My first taste of travel as part of my PhD ( the World Conference on Parasitic Plants in the summer doesn't really count, being held in Sheffield!) ... A visit to the International Syngenta Research Station in Jealotts Hill, Reading.
I admit it's not a huge distance but it felt long enough on the train and a worthy enough journey to break by spending the night at my parents in Knowle. From cosy childhood bed to plush hotel ( on expenses!) where the Complimentary toiletries were so expensive they were bolted to the wall. It was a completely new standard for me at Stirrups Country House Hotel, themed even down to the room Key rings.
Next day, an early start - the taxi whisking us up the gates of the drive. Anne had warned me that the facility was 'in the middle of nowhere' - I hadn't appreciated that this was to the extent that most of the surrounding cottages were owned by Syngenta to house their employees! We were promptly met by Dr David Portwood, who led me on a tour of the site. Although not strictly one of my supervisors, I will be hopefully working with Dr Portwood considerably if I ever get to the stage of generating any data as he has written most of the statistics programmes for analysis. My whirlwind introduction was only really a peek at this company's research capacity: Syngenta employs over 27,000 people in around 90 countries worldwide. Here, the company vision of 'bringing plant potential to life' was realised in the enormous greenhouses and disciplined collections of highly specialised machines whirring away. Although I had hopefully taken my camera, I was warned that photographs wouldn't be allowed. It was quite something to see sugar cane for the first time- the pictures in books don't do the height justice. I especially liked the policy of placing labs next to offices with glass walls in between- a clever way to circumvent the 'no working in the lab alone' rule - as long as a colleague is working late in the office, they can keep an eye on you.
Then it was back to the meeting room to discuss the 'nuts and bolts' of the project. The cultivars for study were chosen, time plans discussed... It is unlikely that I will get down to Jealotts Hill again in the near future as it will take a long time to perfect the MALDI-MS technique for root tissue...especially when it is infected with Orobanche or Striga. So until I get any data there is no real NEED for me to be there....
But I could certainly imagine it, taking a seat in the cafeteria amid the swirl of agronomists, seed specialists, plant breeders, biochemists, molecular researchers,etc discussing the day's progress. My PhD really is the start of a journey and at some point it will take me on to the next chapter. Who knows if it will be here, back at Syngenta?
All too soon, it was time to catch the train back to Sheffield. I really hope to return soon!
Monday, 4 November 2013
This past week has been a particularly busy one for me. I had hoped to make real progress with the Literature Review but, as all my practical work seemed to come at once, this had to go on the back burner for a while. That is a recurring theme in scientific research - the importance of being flexible and to have plans leap out of the window (especially when your supervisor thinks of another useful assay to do)... nevertheless I have learnt many new skills this week, all of which I will need for my project to come.
I have been performing lots of germination assays on Orobanche and Striga, to see which will be the best races to use for the project. It was just as well; one strain of Orobanche was hopeless, with only about 1 in every 100 seeds showing any response to the germination stimulant, whereas another was really excellent, even though the seeds were actually older. I also had a long chat with Anne, whose PhD forms the basis of the work I will be doing, about the statistical methods she used to analyse her data. Oh dear, my head was spinning after that session...
My favourite part, however, was learning how to cut ultra-thin sections with the cryo-ultramicrotome. As I haven't got any infected rice or sunflower roots yet, I was practising on wheat seeds. It is cold work, as the knife is set at 14 degrees below freezing, and also slightly dangerous. "That Knife is so sharp" Professor Burrell (the Mass Spectrometry expert and one of my supervisors) "you will cut yourself before you know it". Such a fearsome blade is necessary to cut the ultrathin sections required for mass spectrometry - only 50 micrometres thick (where a micrometre = 1 millionth of a metre). After mounting the sample, the handle is turned and the sample slowly drops down onto the blade, which removes a section of the specified thickness. Turning the handle then advances the sample by the section thickness, ready to cut the next slice. It was tricky getting used to it - my thin sections kept curling up - but I did manage to mount some on sticky carbon tape in the end. These have been frozen in liquid nitrogen, to use on the MS later.
On Friday, I finally infected my young rice plants with Orobanche. This was a very simple process in the end - the seeds of the parasite are suspended in water and brushed on with a paintbrush. It took several hours though, leaving me exhausted at the end of it. Now the plants are back in their rhizotrons in the growing chamber and I shall leave them for two weeks, during which the unfortunate rice plants will hopefully be invaded by Orobanche. To finish this week, I popped back home to Solihull for the weekend to catch up with friends, family and neighbours, which was wonderfully restorative.
Saturday, 26 October 2013
It seems ironic that, although these parasites run rampant in the countries they affect, it can be surprisingly tricky to grow them in this country, even under the controlled conditions the lab and growth room allow. Nevertheless, the Scholes lab has got this down to a fine art, with precise timings, meticulous watering regimes, accurate chemical concentrations of germination stimulants...etc. I have grown Arabidopsis (thale cress; the model organisms of the plant science world, with the most heavily annotated genome of any plant), Wheat and Sorghum before but working on multiple systems at once is a new challenge. First there are the crops themselves. I have successfully managed to germinate rice seedlings and am growing these up to infect with Striga next week. The problem is, these plants can take up a fair bit of space...hence the rhizotron system. Rather than growing the seedlings in pots, the roots are trained into large, flat square petri dishes packed with vermiculite (which looks like an inedible form of muesli); these are then covered in foil to simulate below ground conditions. The petri dishes are packed together in trays, the young leaves poking out of a hole at the top, each with a "dripper" for irrigation. The Striga seeds, meanwhile, are prepared in an incubator in the lab; like Orobanche, these require a few weeks of "pre-conditioning" - being coddled in warm, moist conditions. This makes them responsive to germination stimulant. Because parasite seeds are tiny (no, really, miniscule, like dust!), they have little reserves so have developed a clever strategy where they only germinate in the the presence of a suitable host that they can rapidly infect. To do this, they have evolved the ability to recognise chemical compounds naturally secreted by hosts in the root exudates, called "germination stimulants". In the case of Striga, these compounds are classed as "Strigolactones", which also have a role as a plant hormone in the host, to regulate branching. The parasite seed then germinates and follows the concentration gradient of the germination stimulant to reach the root. Synthetic strigolactones are available; we use one called GR24 to pre-germinate the seeds before infecting the plant. This is done by prising the lid off the rhizotron and literally "painting" the seeds over the roots. The poor rice plant hasn't got a chance. At this moment, my Striga seeds are still preconditioning in the incubator and my rice plants propped up in their rhizotrons in the controlled growth room chamber, ready for infecting next week. I mustn't forget I'm on water barrel duty this coming week - if everyone's plants die from drought it will be my fault!
Meanwhile, I am constantly surprised at how much there is going on (perhaps Durham was a bit of a small University in that respect...)... it can be a bit overwhelming at times and I had to be disciplined in NOT attending all the talks at the book festival. I did catch a highly entertaining talk on science communication given by Ed Young, famous for his Blog "Not exactly rocket science" - it certainly gave me a few ideas for shaping this blog. The Animal and Plant Sciences Department, meanwhile, is keenly committed to public outreach, with a highlight this term being the "Christmas Time Lecture" where close on a thousand young school children are treated to a "Royal Society Lecture" experience before hands-on demonstrations and other entertainments. Past topics have included Birds and Dinosaurs and this year Plants have the starring role... I'm keen to be involved but with this literature review hanging over me, I'm not sure I will be able to spare the time to organise a demonstration so perhaps it will have to be as a steward. It will be worth it to see the unveiling of RoboPlant!
Monday, 14 October 2013
1. My bench in lab C45
2.The wonderful collection of fridge magnets in the lab
Saturday, 5 October 2013
That aside, the project itself sounds very exciting. My first tasks will involve becoming familiar with growing parasitic plants to take sections from. Apparently, it can be very difficult to infect sunflowers with Orobanche in the lab- usually in agriculture, the problem is that crops are too EASILY infected. However, this lab contains the world experts in Striga and Orobanche and over the years they have developed tried and tested protocols. I will be benefitting from years of hard earned experience!
The growing facilities will be closed down over Christmas for maintenance so I will have to start preparing specimens straight away to have them ready in time. My Maine ask for is term however, is to produce a Literature Review to place my project in the context of work already performed by others ( with so many research labs in the world these days, it is all too easy for different groups to replicate one another's work). Fortunately, I had to prepare a Literature Review as part of my final year at Durham - I chose to compare the similarities between plant interactions with mycorrhizal fungi and nitrogen fixing Rhizobia bacteria- so am familiar with the paper trail that chasing references entrails. Besides the wonderful, yet occasionally frustrating, referencing software Endnote. It's difficult to know where to start, so I shall just have to dive in and hope that the way ahead will seem clearer as I read...and read... and read....
This week has been a whirlwind of registration tasks and compulsory training sessions, everything from fire safety to waste management. 'At one point we had 27 separate waste streams' the Deaprtmental Technician cheerfully stated 'but that was a bit too much to manage'. There still seem to be an awful lot though, with different boxes and bins depending on whether your waste is hazardous, medically related, infectious...etc. Being so used to science paraphernalia, I find it hard to believe that pipettes tips and latex gloves still require special disposal as these count as 'offensive waste' which could upset members of the public if they came across them. Meanwhile, after the CoSHH ( care of substances hazardous to health) session, I feel that I will be lucky to get any actual research done, with the number of Risk Assessments I will need to do!
More excitingly, I have a desk, a locker and a bench to work at. Now I can feel like a member of the lab, even though I still don't know who everyone is and have forgotten the names of those who I was introduced to. The sooner the promised lab photo board is produced the better! And I have attended my first 'Wednesday morning coffee break', held in the departmental common room at 10.30. Coffee break happens every day, but everyone goes on Wednesday because there are free chocolate biscuits. Apparently, it was the only way to get everyone in one place so that any important announcements could be made...
Hopefully by my next post I will have made some progress with the literature and learning names! Thanks for reading!
Sunday, 8 September 2013
I found the experience particularly valuable this year as the talks allowed me to gauge what the Gatsby supported PhD students had achieved after one year, two years or even three/ four years. This helped to give me an idea of the rate of progress expected from me when I start my PhD in October. The stand-out talk for me however, was given by Professor Hagen Bailey, of the Department of Chemistry at the University of Oxford. Completely eschewing a plant science theme, he described how "nanopore" technology could revolutionise DNA sequencing. This technique involves introducing membrane pores based on alpha-hemolysin from Staphyloccus into a chip, and feeding DNA through these channels. By incorporating a nuclease which cleaves off bases one by one as the DNA strand emerges or inserting a base reader into the channel itself, the sequence can be read. This avoids the need for using fluorescent bases (required for most sequencing methods) and can be fashioned into arrays with thousands of pores, ultimately capable of sequencing the human genome in 10 minutes. Given that this would be the equivalent of reading a thousand copies of War and Peace, this is quite impressive! Professor Hagen also described how these pores could be used to connect aqueous droplets to form "minimal tissues", which could have potential in organ enhancement or replacement. An intriguing diversion from plant science and an exciting topic to follow in the future...
I must confess that I do enjoy the "Oxford experience" that the meeting gives me - staying in quirky college rooms (no piano this time, but still lots of random doors and a fireplace), listening to the clock bells chiming out over the city at night, the formal evening dinner... I did feel sorry for the vegetarians this year however, who instead of being served "prawn and avocado cocktail" had to make do with "avocado...and more avocado ". I'm already looking forward to the next meeting, and who knows? Perhaps I will be presenting something myself...
Saturday, 27 July 2013
How has this week gone so quickly? On Monday, I felt that it would surely take a short lifetime to work through the programme of symposia, plenaries, poster sessions...similar to the feeling I had on starting nursery school, with all those years of compulsory school education stacked up before me. Yet, here we are and I am still surprised to find that I am actually now a 20-something university student and that IUPS 2013 is nearly finished.
But there was still time to be truly inspired, as Professor Karl Deisseroth's lecture "Optical deconstruction of fully-assembled biological systems" demonstrated. The audience were treated to an impressive brain-imaging gallery produced by the novel CLARITY technique, where brain lipids are replaced with a hydrogel framework that allows super-resolution fluorescent imaging. For anyone with an interest in neuroscience, this is a hot topic to read up on. Practical applications of this stunning technique have been limited however, due to the massive data sets generated. Hence, Deisseroth moved on to describe the latest results from the more established technique of optogenetics - where the transgenic introduction of channelrhodopsin allows specific neurones to be stimulated in response to light. This is being used in an intriguing set of experiments where mice are placed in a cylinder half filled with water. At first, the mice swim vigorously as they search for an escape, then they become more quiescent; researchers are hoping to identify the neurones that mediate this transition from active to passive resistance. Preliminary results indicate that neurones of the medial prefrontal cortex are selectively inhibited during this behavioural change and that stimulating these with light can re-induce active swimming. This simple model is complicated, however, by indications that these neurones change the information they represent according to the level of dopamine. It may be that optogenetics, rather than generating straightforward answers in the immediate future, will instead reveal a further dimension of complexity...but this appears to be a reoccurring theme in biology (think of DNA and the gene-->RNA-->protein "dogma").
"...a scientific programme that has brought people from all over the world and stimulated our interest over the past five days..." Denis Noble
After the applause abated, the proceedings moved swiftly to the closing ceremony. IUPS President Denis Noble celebrated the "massive expansion of membership", including Bangladesh, Malta and Nepal. IUPS 2013 also bore the distinction of hosting the largest delegation from Africa so far and for being the first IUPS conference to receive delegates from North Korea. Reference was also made to a comment by the Nobel Laureate James Black at the 1993 IUPS conference in Glasgow that we would see "the progressive triumph of physiology over molecular biology". This might seem counter-intuitive, given the explosion in the field of genetics and molecular biology, however Denis Noble stressed that this was not predicting the replacement of the one science with the other - rather, physiology would be the medium which brought new molecular insights together into a cohesive whole. Bridgette Lumb then extended thanks to the wide number of international organisations and commercial companies who had supported the conference, giving a staggering final figure of 3068 registered attendees.
"...a great and unforgettable meeting...with an atmosphere of friendship and collaboration..."
Benedito H Machado, Organising committee for Rio 2017 "Rhythms of Life".
And then what we've all been waiting for! The grand handover - will this involve flag waving, Brazilian Samba dancers, glorious pyrotechniques? No...a rather more muted affair yet more fitting as the Brazilian organisers emphasised the importance of friendship and collaboration, and extended a sincere invitation for all to join them in Rio 2017 at "Rhythms of Life". A short video, carried throughout by a stomping Samba soundtrack, whetted the appetite with images of an exotic, dynamic city exuding charisma. Finally, the IUPS 2013 organisers gave us one last treat - a round-up movie showcasing the "best moments" of the conference including the delegates' table football skills, dance moves and drunken antics... I do hope they got that man out of the canal....
It's certainly been an experience although I feel some regret that I will probably be unable to join the conference in Rio...but I am sure that the field will have progressed into even more exciting domains by that point.
So it's goodbye from IUPS 2013!
Thursday, 25 July 2013
But we're not very good at it, as shown by our failings in poker and romance. Nevertheless, advances in brain scanning technology, such as PET and MRI scanning, are allowing scientists to 'correlate physical changes in brain states to changes in subjective mental states'. The questions of what this could potentially be used for, and by whom, were discussed in the symposium 'Brain Imaging - An Ethical Time Bomb?'. Companies already exploit emotive reactions when promoting their products - think of McDonalds Happy Meals and luridly coloured sweets for children. It is a scary thought that companies could commission research to understand how to further stimulate cognitive pathways. One researcher even said her group had been approached by a gambling company asking how they could make the appeal of winning £1 outweigh the frustration of loosing £100. Could political parties use brain scanning technology to understand how to manipulate our emotions towards their agendas? Professor Hank Greely, a Professor of Law at Stanford University, asserted that the main use of brain scanning technology in the immediate future would be for prediction. This could have great potential medical benefit: apparently PET scans are now capable of detecting the build up of amyloid plaques that are the hallmarks of Alzheimer's. But this throws up a new snarl of dilemma - if you could have a test for dementia, would you take it? And if you did, who would you tell? Could health insurance companies or employers demand the result of a test if they knew you had taken one? Could they force you to have a test themselves? Given the considerable pressure companies are under to avoid discrimination ( such that they can't ask women if they plan to become pregnant), this seems unlikely, at least in small scale companies. It is more likely that brain scanning will take a dominant role in the courtroom, as a tool to predict the likelihood of re-offence. Greely was keen to stress that, even if these methods aren't 100% accurate, if they are more reliable than current methods (e.g. a defendant's say-so) then they may still be useful. How the information is presented could have a major effect however: a fluorescently coloured brain scan image is much more striking to a jury than a dry report read in a monotone. The issue of lie detectors was also raised - in the USA one can pay to have a test done privately which tests responses to a chosen list of questions. But if the result if unfavourable, the test company will conveniently forget it, allowing defendants to choose what to present in a court as evidence for their case. Greely described how brain scan imaging could be a potent tool in deciding cases where the claimant states they cannot work due to excessive pain. Can a court order someone to have a brain scan? Is there a 'human right' to not have a scan against a person's will?
By far the most impressive aspect of this talk however ... it was given WITHOUT powerpoint slides! And intentionally (not due to equipment failure)! Very admirable in this age.
Wednesday, 24 July 2013
But does it work?
A considerable audience gathered to hear Dr Krista Varady's lecture 'Alternate day fasting: a novel dietary restriction regimen for weight loss in humans' which described the results of a pilot trial in the USA. In this study, 20 obese makes and females took on a regime where, for three days a week, dietary intake was limited to 25 % of their needs. This was imposed over 8 weeks: for the first 4 week block, the patients were 'control fed' (as it wasn't thought that they would be able to calculate a 500 calorie meal themselves) and for the second half of the trial, they prepared the 'fast day' meals themselves, using dietary advice. I was impressed by what a 500 calorie meal amounted to - a vegetarian pizza, an apple and a handful of peanuts. I would struggle to eat that over a two hour period, which the participants were required to do. Then again, if it was the only meal you had that day...
Only four participants dropped out of the study and at a fairly early stage. The remainder lost an average of 5.6 kg with the rate of weight loss being fairly steady throughout. Nevertheless, in traditional dieting regimes ( especially those involving no additional exercise) this weight loss is usually lean muscle, rather than fat, which reduces the amount of metabolically active tissue, making it even harder to loose weight. In THIS case, however, about 90-95 % of the loss was attributable to fat. The subjects also lost about 4cm of their waistline, lowered their systolic blood pressure by 6 mmHg and reduced their LDL cholesterol levels by 20-25%. Subject compliance, as assessed through feeding diaries, was 87%.
But what was happening on the 'feed days'? One would presume that there would be a temptation to binge...similar to the pancake syndrome before lent. These participants, however, were found to only consume 110% of their energy needs and so didn't make up the deficit. Many of them were even happy to carry on the diet with Varady stating that 'after the initial two weeks most have no problem with the fast days'. Some of the audience were sceptical about the long term effects and Varady admitted that the rate of weight loss did seem to drop after 24 weeks. Perhaps this is only to be expected though- one can't keep going down forever. The most striking thing to me was Varady's self-confidence in the technique 'I do this a couple of times a year after holidays to shed a few pounds'.
Are you on the 5:2 diet? Do you apply it to anything else? Please comment below!
This was followed by an brief discussion by Gaelle Boudry on how neonatal gut development can be influenced by milk composition to the extent that this has repercussionsfor later life. Piglets fed on high protein breast milk showed a delayed barrier function ( increased gut permeability) and disrupted immune responses. Quite disturbing when human milk formula compounds during the 1980s had protein levels in excess of those in normal breast milk.
Tuesday, 23 July 2013
IUPS 2013 The Public Lecture: The Rhythms of Life – What your body clock means to you from eye disease to jet lag
Speaker: Professor Russell Foster, Professor of Circadian Neuroscience at Oxford University and a Fellow of the Royal Society. A passionate advocate for communicating science to the public, with a strong YouTube presence.
Monday, 22 July 2013
David Dewhurst, of the University of Edinburgh gave an evaulation of online medical programmes offered by his institute. He described how online scenarios could allow students to conduct 'experiments' that they couldn't otherwise do, working on tailored 'virtual patients'. This certainly has the advantage of avoiding costly and time consuming ethics procedures. Not ALL practical skills can be learnt online though - a fish dissection I did in my second year springs to mind. But online resources can certainly be useful in supporting limited wet lab sessions. In this case, watching a video uploaded onto the University online network was invaluable - when practicals are typically hectic, cramped, rushed affairs with the demonstrators struggling to turn everybody out after three hours, any advance preparation helps the experiment to go more smoothly, allowing students to learn more from the experience. perhaps a good example of online/ practical complementation is the 'Hazard Perception' element of the driving test. Exposing learner drivers to these situations ie real world would be frankly dangerous, yet it cannot replace the practical 'hours behind the wheel' ( more like days in my case) needed to master the skill.
Sunday, 21 July 2013
Key point: "We need to focus on the management of information to understand biological complexity".
As a researcher of molecular mechanisms governing cell function, Sir Paul Nurse may not be an obvious choice to open a Physiology Conference. He argues otherwise, however, stating "I'm always a physiologist - I want to understand how cells function, how they work, using whatever tools are available". He highlighted the importance of physiology using the Oxford English Dictionary definition "a branch of science that deals with the normal function of living organisms and their parts..." - in his view this encapsulated the central quest of biology. The second part of the definition bothered him however - "...in so far as it is not dealt with by more recent sciences". This gives the impression that physiology is merely there to "fill in the gaps" left by molecular biology, immunology, genetics, etc. Instead, Nurse argued, these other fields enhance our understanding but cannot substitute for physiology in meeting the key aims of biology. Having established the importance of physiology, he now asked: Where is this science going?
In the second part of the lecture, he emphasised how living organisms can only be understood as networks of interacting components, stating that higher order processes (such as homeostasis) can only be understood as the result of the gathering, storing and processing of information by a system. He cited DNA as an example of this- essentially a digital storage device. In addition, the Lac Operon (a genetic "switch" mechanism modulating metabolic control in E. coli) provides an exquisite instance of a negative feedback system, which responds to a flow of information. Future advances in physiology must be based on translating the chemistry of systems into modules that manage information. Nurse was keen to draw a distinction between metaphors relating biological systems to electronic machines or circuit boards, the key difference being that these are "hardwired" whereas biological systems are "wet wired" - the components can be connected differently to change the information received. Information processing was so central to biology, he argued, that understanding how complex networks function in general - including models of airport hubs and ecological or sociological networks - can illuminate aspects of the physiology of cells & organisms. He rather daringly stated that our thinking must be more "feminine" - the point here being that men are supposedly more simpler systems, being "either off or on" whereas women have more complex constitutions. Rather than considering biological systems as simple, linear, input-output pathways, we must imagine an intricate network with superimposed levels of feedback control. Key questions to address in future include how the flow of information through such a system can generate fine spatio-temporal control, and how introducing dynamics can allow a greater degree of information to be transmitted. A formidable challenge is to place these complex systems within the evolutionary context. Nurse described the case of "John Harrison's clocks" who developed a series of machines to measure longitude in response to a commission from the English Admiralty. Each of these was intelligently designed and used to inform the development of the next with the clockmaker able to go back to the drawing board and start from scratch between each prototype. Biological systems, Nurse stated, do not have this luxury - they must carry the remnants of their evolutionary history. This constrains evolutionary development, rendering many physiological phenomena inefficient or redundant. As a result, "complexity may lead to counter-intuitive explanations" and we "cannot assume that the simplest explanation will be the adequate one" in each case. Nurse related this to physics, where "when dealing with the very big or very small, we are lead into the increasingly bizarre". Similarly, the evolutionary complexity of living systems may draw biology into "new worlds of strangeness", away from what we can understand counter-intuitively. This may require increasing assistance from mathematicians and physicists to understand a new level of abstractness. Nevertheless, Sir Paul Nurse's message was clear; physiology can only advance further if it embraces a view of living organisms as dynamic, intricate systems responding to a constant stream of information.
"Physiology moves back onto centre stage: a new synthesis with evolutionary biology"
Denis Noble CBE FRS. About: Eminent researcher in cardio-vascular physiology, current president of the IUPS.
Key point: New insights in physiology are exploding the traditional concepts of Neo-Darwinism evolutionary theory, and opening up a new world of hereditary mechanisms.
"If physiology has moved off centre stage, it is coming back with a vengeance".
"The genome is an organ of the cell, not a dictator. Control is distributed".
The focus of this lecture was in demonstrating how the classic views of evolutionary theory are being pulled apart by new physiological advances. According to Neo-Darwinism, evolution is primarily gene-centred and occurs through the gradual accumulation of random mutations. According to the Weismann barrier, the germline is completely isolated from the parent, hence there is no possibility of acquired traits being inherited. Noble first asked "Are genetic mutations actually random"? Current evidence indicates that genetic mutations follow distinctly non-random patterns throughout the genome. An example of this is P elements, DNA transposons in Drosophila fruitflies - demonstrated to hone in on functionally related areas as they jump between parts of the genome. Noble then explored whether evolution only occurs through gradual assemblies of single mutations. Analysis of the draft human genome sequence in 2001 indicated that the evolution of transcription factors and chromatin binding proteins could not have proceeded one amino acid at a time - rather whole areas and domains must have been shuffled to obtain the current conformation, indicating that mechanisms of reconfiguring the genome must exist. This was illustrated by the example of domestication, a process of introducing changes gradually through generations. However this form of selection "has never led to the formation of a new species. It is a purifying force, not a creative force". Compare this with hybridisation, which involves mixing up two distinct parental genomes. Noble also described how our very concept of a gene has changed and the classic linear progression of DNA --> phenotype has been abandoned in favour of a three way interaction between DNA, the environment and the phenotype via a biological network. This explains why knocking out genes rarely reveals their function as the network can compensate for their loss. This was demonstrated effectively by Hillenmeyer et al. who showed that approximately 80 % of knock out gene mutations in yeast are silent unless additional environmental constraints are imposed.
Noble then moved on to ask "Why should a physiologist be concerned with evolutionary biology?". Traditional evolutionary views are gene centred, yet physiological research is demonstrating that organisms can "immune themselves from the genome". Furthermore, information transmission is not a one-way process as organisms can impose downward control onto DNA through cell signalling, transcription factors and epigenetic modification. An example of this is provided by work on rats showing that regular grooming in early life makes the mature adult less fearfull - is grooming time limited in colonies stressed by predation or starvation? Another exciting illustration is the production of cross species fish by placing a carp nucleus into an enucleated cell from a goldfish. In the rare circumstances when this produces an embryo, the skeletal configuration is intermediate between the two, but much more similar to the goldfish. Hence, information cannot be transmitted solely by the DNA but must be influenced by maternal factors in the egg cytoplasm. Work on the nematode worm C.elegans meanwhile, has revealed that epigenetic changes can be incredibly robust. Here the inheritance of antiviral RNA molecules was demonstrated for up to 100 generations, even though the DNA template had been lost; inheritance had been achieved through RNA polymerase amplification in the cytoplasm. Our view of the DNA machinery should echo that of Barbara McClintock, who viewed DNA as a highly sensitive organ that can detect and respond to unexpected events. Noble cited how genome reorganisation may also occur through the lateral acquisition of new DNA material from unrelated cells, such as the ingestment of the prokaryote cells which became reduced to mitochondria and chloroplasts. The central concept of this stimulating lecture was clear: the genome is NOT isolated from the environment and furthermore, acquired characteristics can be inherited. Perhaps Lamarck wasn't so wrong after all.
From the outside of the ICC Exhibition Centre and Symphony hall , there is little to bely that the major event in the Physiological Sciences Calendar - the 37th International Congress of Physiological Sciences - is on the brink of launching. Inside however, the flow of international arrivals, babble of foreign tongues and dynamic mixing of reunited colleagues is reminiscent of a thriving airport, as is the long line of "check in" desks, where badges and conference packs (containing an impressively stodgy abstract book) are being rapidly distributed. I particularly like the stairwell listing the previous venues - it gives a feel of continuity as one ascends to register. As one familiar with the Birmingham area, I wonder what impression "the city of a thousand trades" has had on the foreign delegates. In the Opening Address, Professor Bridget Lumb, Chair of the Organising Committee, sets the event in context through some select statistics; 2020 abstracts submitted, 535 lectures, 202 symposia and over 700 speakers, not to mention industry sessions, workshops and the public outreach activities. What really strikes me, however, is that this singular event has been in the planning process for eight years, on a par with the Olympic Games. Professor Walter Boron, Secretary General of the IUPS emphasises how such events don't happen through "the random aggregation of particles" but rather rigorous and comprehensive preparation. It is thrilling that the congress has arrived again in the UK, the last time being in Glasgow twenty years ago. Professor Jonathan Ashmore, President of the Physiological Society, outlined the historical presence of the congress and how the event had consistently attracted the leading physiologists of the time. This was portrayed succinctly by a photograph of delegates at the 1923 gathering in Edinburgh, which featured, among others, Ivan Pavlov, Edward Sharpey-Schafer (a pioneer in endocrinology who gave us the word "insulin") and Archibald Hill (a founder of Biophysics). Such an introduction lent a natural progression to the opening lecture, given by Sir Paul Nurse, winner of the 2001 Nobel Prize in Physiology and Medicine for his research which identified the protein components which regulate the cell cycle. The opening event had a refined, restrained feel - there was no attempt to enforce awe through special effects or overbearing graphics. Instead, the palpable excitement tingling in the audience as the lectures started made it clear that this was a group who had converged from all corners of the globe to hear great science and discuss it - and that they were very much looking forward to doing so. Bring on the next five days!
This was one of my favourite sections of the meeting and is a topic close to my heart. Here are some of the highlights for me from the session:
Precision control for Orobanche: The herbicide Glyphosphate can be used effectively to control Orobanche, yet can also induce damage for the host & environment and is expensive for small-scale farmers. Extensive studies in Carrot (a major crop in Israel) have identified that applying low doses of herbicide at 600 growing degree days (an early stage of Orobanche development) is the optimum time for treatment; later applications are significantly less effective (Cochavi et al. Neww Ya'ar Research Centre, Israel). Such "precision timing" enables limited stocks of herbicide to be exploited to their full potential, whilst minimising host damage. But how to estimate the developmental stage of a below-ground parasite? A comprehensive study of Orobanche infestation of tomato in Israel demonstrated the potential of mathematical modelling to address such issues (Eizenberg et al. Newe Ya'ar Research Centre, Israel). For irrigated crop systems, the main constrain on Orobanche development is the soil temperature , rather than moisture availability. In this project, a "drone" device was used to provide aerial mapping of the infected fields - the images provided such good resolution, that the infection stage could be visually assessed (whilst avoiding the need for laborious ground-level assessment). By correlating this to real-time soil temperature data, a model was formulated which could calculate Orobanche development based on the soil temperature. Hence, these methods can empower farmers with the knowledge of when the parasite is most vulnerable to herbicide treatment.
Combining resistance to drought and Striga: when considering methods for parasite control, these should not be isolated from other environmental or biological challenges constraining production. This was demonstrated superbly in a study which quantified drought tolerance among cultivars developed originally for Striga tolerance (Menkir et al, International Institute of Tropical Agriculture IITA). Striga itself is adapted to thrive in regions erratic rainfall and plants weakened by drought have been shown to be more susceptible to infection. The most drought-tolerant cultivars were crossed to produce hybrids, some of which demonstrated an incredible yield increase under infestation conditions (in one case 4113 kg/ha compared to 875 kg/ha for the parent line). As the speaker noted, selecting for these plants could address the dual problem of low moisture availability and parasite control in a way akin to "carrying two goats on the same motorbike" (the image helped to explain this!). Nevertheless, it was noted that the selection mechanism may simply be for higher yielding lines if the relative loss of yield between well irrigated/drought or uninfected/Striga infested conditions was the same as that experienced by the parents. Based on the significant differences in yield however, I'm not sure the farmers themselves would be too concerned about this point.
Arbuscular Mycorrhizae to the rescue? Having based my final year Undergraduate literature review on Arbuscular Mycorrhizal Fungi (AMF), I am perhaps slightly biased towards their intricate lifestyle and benefits. These fungi form intricate symbioses with most plant species, providing nitrogen and phosphorous in return for photosynthate sugars; the development of this association was thought to be instrumental in allowing plants to first colonise the land. Louarn et al. (INRA, France), have demonstrated however, how AMF may also have a practical use in controlling agricultural parasites. Strigolactones are produced by plants to recruit AMF but these have also been exploited by parasites to induce germination (allowing parasitic seeds to remain dormant until an available host is in close proximity). AMF colonised sunflowers were shown to be less susceptible to infection by Orobanche, yet this may simply be a consequence of decreased strigolactone production (if the roots are already colonised, the need to recruit AMF is reduced). In accord with this, root exudates from AMF colonised roots show lower germination stimulation of Orobanche than non-colonised root exudates. However, complementing the AMF root exudate with the classical synthetic strigolactone GR24 did NOT fully restore germination to the level of application of GR24 alone, suggesting that AMF produce a germination inhibitor which passes into root exudates. Characterising this inhibitor could offer an exciting avenue of research into parasite control, at least for Orobanche cumana.
Finally, the most popular talk was "Shoot the mistletoe", which described the development of a novel mistletoe controlling device at the University of Sao Paulo, Brazil. Gregorio Ceccantini humorously described how, at a different scientific gathering, involving considerable consumption of alcohol, an idea was born to use an air-triggered paintball gun to fire pellets of herbicide at mistletoes attached to commercially important trees. Besides proving that scientists love their toys (also justified by the "drone" study above - we were treated to many videos of it in action), this method does actually seem to be effective! Perhaps a way for bored teenagers to work off aggression?