Philip Campbell - The Future of Science Communication
I only arrived for the end of this talk but it seemed like he'd put thought into it and had lots of substantive ideas. BUT he's the Editor-in-Chief of Springer Nature and apparently he basically didn't mention open access at all (?!). This was right after news of a possible huge EU rule saying all EU-funded researchers have to publish open access, and of course open access has been a huge issue in science for ages - how do you just ignore that?
Nick Lane - The Future of Bioenergetics
I loved this talk! He gave some lovely quotes about bioenergetics:
- Schrodinger saying an organism maintains itself at a 'fairly high level of orderliness' by 'continually sucking orderliness from its environment', which was quite prophetic even though we'd now call it entropy and say it the opposite way around.
- A beautiful one from Peter Mitchell, who proposed the chemiosmotic theory of oxidative phosphorylation:
'I cannot consider the organism without its environment … from a formal point of view the two may be regarded as equivalent phases between which dynamic contact is maintained by the membranes that separate and link them'That quote is so gorgeous it makes me emotional. The implications! Man I love biology so much. Fun fact, while searching for the full quote I found it in this paper and now I'm really excited to read the paper because wow, what a cool topic - 'Bioenergetic Constraints on the Evolution of Complex Life'. And it turns out to be by Nick Lane himself! This is so exciting.
ANYWAY.
Lane's talk was a whistle-stop tour through various aspects of bioenergetics and occasionally he lost me because he just went so fast, but overall it was amazing. Early on he talked about ATP and how it's not its bonds that are special, it's the displacement of its concentration from equilibrium, which shows him as a man after my bioenergetics lecturer's heart and brought me right back to my beloved Metabolism module. I understand why people consider it the hardest one, I definitely found it difficult at first, but when I really threw myself into studying it for Schols using Lehninger I just absolutely fell in love with it. The flow of energy through it is my kind of spiritual experience.
[Also, Lane said that the famous Peter Mitchell actually did like none of the lab work - Jennifer Moyle did all that. So thanks for giving the woman a shoutout.]
Lane talked about the origin of life and the similarities between inorganic deep-sea pores and cells, and then showed a diagram similar to this which was such an awesome way to think about endosymbiosis that it's one of my main takeaways from the conference. Bacteria and archaea diverging separately from the Last Universal Common Ancestor and then meeting later to form eukaryotes - a reunion in the Tree of Life! It may only be possible to show it visually using this very simplified form of the tree but I love this way of thinking about endosymbiosis, of an archaeon and a bacterium joining together and forming a eukaryotic cell with mitochondria.
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| E = Eukarya, B = Bacteria, A = Archaea. There would also have been other crossing(s) with plastids but this is the main one. Made using paintsomething.co |
Lane talked about how bacteria and archaea are virtuosos of metabolic biochemistry (and they really are - have you seen how many ways bacteria can extract energy from the environment? And archaea's adaptations to heat?!) but they're still constrained in morphology. Eukaryotes could diversify into all the wonderful kinds of plants and animals we see today because they had mitochondria to provide more power.
Huh, if that's true it means that if the chance endosymbiotic event had not occurred, the whole world would still just be unicellular organisms. Weird to think about.
He also talked about strong selection based on the two genomes in the eukaryotic cell (nuclear and mitochondrial) having to work together, and also talked about why there are two sexes and why mitochondria are only passed down from the mother, saying uniparental inheritance of mitochondria increases variance between zygotes, facilitating selection by eliminating cells with badly mutant mitochondria.
He talked about how organisms that don't exhibit germline sequestration have low mitochondrial mutation rates and vice versa, and then mentioned that contributing to the Cambrian Explosion. He didn't explain, but I guess it may have been about the different kinds of body plans that resulted from finding ways to sequester the germline.
He showed an interesting slide about proteins encoded by the mitochondrial vs nuclear genome being extremely intertwined in the cell, literally wrapping around each other and physically working together.
His talk then got a bit disjointed and harder to understand. He talked about the interconnection of things, like how failure to oxidise NADH blocks the Krebs cycle, leading to no energy and no biosynthesis of all the other biomolecules that come from the Krebs cycle, about diving turtles who go under water for long periods of time without air and so succinate accumulates, binds to HIF1alpha and changes gene expression. On reperfusion of oxygen, succinate produces free radicals which can apparently lead to stroke. If the genes in the mitochondria and nucleus don't match, a similar block can occur.
He then talked about some of his own research on a chemical abbreviated as NAC (N-acetyl cysteine I think) suppressing stress in testes and increasing it in ovaries, and being lethal in some cases of mitochondrial incompatibilities but fine in others. Females get into a dire state with high NAC whereas males are fine, and these differences between individuals can be looked at using metabolomics.
There was also this:
'I never realised how stressed my testes must be.'
and from the chair at the end:
'Thanks Nick, I hope now that your talk is over your testes are less stressed.'
Emma Teeling - The Future of Zoology
Emma Teeling was brought on as a replacement for someone who dropped out last-minute and I am so glad because her talk was amazing and I got so excited and wanted to research the topic by the end. The start of the talk wasn't great in my opinion, but once she got to her research (into bats and longevity) it was brilliant. She showed a graph that I have crudely reproduced (the 130 was actually like 150 but I didn't want the scale to be even more wrong):
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| The green line shows time of onset of age-induced morbidity. |
So she was talking about a projection that children born today could live to 150, and showing that unless we deal with age-induced morbidity i.e. sickness as well as just mortality, that'll just result in more years spent sick and infirm. Healthspan is important, not just lifespan.
Then she showed us 'Methuselah's Zoo', which contains animals that live for hundreds of years. But these are typically marine animals that live slow, cold lives and some don't reach sexual maturity until the age of 150. So, if we want to learn about human longevity, we should look at mammals. Bats buck the body size-longevity proportionality trend; of the 19 species of mammal that live longer than humans given their body size, 18 of them are bats (the remaining one is the naked mole rat). And they don't live slowly, they're the only mammals with self-powered flight. Live fast, die old.
To try to find out how bats do it, Teeling and students captured 700 bats a year and recaptured them each year (since they can't be kept in the lab) to take samples, and developed methods to figure out the bats' secret. She showed us a figure that she said was unpublished and was the result of 8 years work, saying that the secret is that bats repair their DNA more as they get older. According to this press release I looked up, they also don't do it using telomerase, so it doesn't risk cancer, and they barely seem to get that.
She made a pretty good case for zoology as a source of ideas a la 'Evolution is cleverer than you are' (Orgel's Second Rule).
I now kinda want to find out how bats repair their DNA more as they age, and also am wondering what sort of age-related morbidity they get, if any.
But anyway Lane and Teeling's talks consecutively got me very excited and were my favourite of the conference, probably followed by Ben Feringa's.
Aoife McLysaght (Chair)
I haven't mentioned the other chairs but I love Aoife, my supervisor and Head of Department, and would like to say she did a good job. I also loved how she told Mark Ferguson (head of SFI) that he should fund basic research. Hehe.
Applause from #whatislife75 audience for @aoifemcl highlighting importance of basic research funding to SFI's director Mark Ferguson in attendance. pic.twitter.com/ONfVaksBkb— Alan Rice (@alanmrice) September 6, 2018
Kathryn Holt - The Future of Infectious Disease
This talk would've been my dream last year but for some reason I've kind of gone off infection as an area of study. It was a solid talk though, with some interesting parts like this proposal to combat antibiotic resistance:
Super interesting - combating antimicrobial resistance by designing drugs so that the more a bacterium adapts against one drug, the more effective Drug B is against it. #whatislife75 pic.twitter.com/ZKXfCOmf3T— Elle Loughran (@frizzyroselle) September 6, 2018
Holt also talked about using phylodynamics to model the Ebola outbreak, which was cool because Dan Bradley taught us that in the Genetics section of our Infection & Immunity module. A vote of confidence in the 2nd year Biology curriculum!
Ottoline Leyser - The Future of Plant Life
I wish Leyser was my lecturer, honestly. She was such a good speaker while staying still and speaking precisely, being witty without explicitly cracking a bunch of jokes. Definitely added to my growing respect for plants.
She started by talking about plants' remarkable ability to build themselves almost out of thin air, and about the van Helmont willow experiment, in which he showed that trees did not in fact grow by eating soil but by drinking water (though of course he didn't get it quite right). When plants moved out of the sea and onto land, sex was a lot harder because gametes couldn't just be dispersed through the water, and so plant bodies had to specialise. Their development of roots put a huge constraint on them; they were a sitting duck in a changing environment and amongst predators, threatened by snails, which couldn't predate anything that could move with any speed at all. So plants need developmental plasticity and to develop a modular body plan, with flexibility of form, continuous growth and development, and no unique parts. For example, there's a new shoot apical meristem filled with stem cells at the base of each leaf, which is good as the main apical meristem, so if one part is eaten they have backups. Chopping the main shoot off, i.e. pruning, activates dormant buds and allows the plant to regenerate.
What all this means is that plants constantly face decisions, and the one Leyser studies in particular is the decision to adjust amount of branching based on nitrogen supply. Plants branch more when they have more nitrogen, and vice versa. Some might say that this is a trivial decision based on whether or not they have enough nitrogen to build branches, but it isn't; when nitrogen is low, growth is directed to the roots to maximise the amount of the rate-limiting resource.
To investigate this, she used a classical genetics approach and found a mutant with a one-base-pair change that branches lots even when low on nitrogen (though it does end up being quite short as it's struggling for nutrients), showing that it's a decision rather than just directly resource-limited. She's still working on figuring out what the bp change does but it's in an enzyme that, if I recall correctly, ocidises carlactone to carlactonic acid.
She then talked a bit about human needs in agriculture and how those clash with natural selection, e.g. in agriculture we want nice, digestible seeds that are left on the plant so they're easy to harvest, whereas natural selection guides the opposite of that.
In terms of the future of plant science, she said we need to move beyond just studying parts and look at the dynamics of the system; physical parts are easiest to understand, but we need to understand input-outputs and how things are passed through the scales from molecular to cellular to meristem to plant, and potentially recast this time-series data into parts, which are more intuitive, e.g. biological switches - are they rapid/gradual, easy/difficult hysteresis, is the input-dose response a threshold/continuous model? We need to understand the flow of information throughout the biological system to intervene in a sensible way.
I really enjoyed this talk. Also, hell yeah, genetics features in nearly all of these.
Michael Rosbash - The Future of Fruit Fly and Circadian Biology
Rosbash got the Nobel recently for discovering (some of) the genetics behind circadian biology. He postulates that the purpose of the circadian clock is to allow us to anticipate external events and perhaps to govern internal coherence. He said that there are different circadian clocks in bacteria, plants and animals, which points to multiple origins and the clock serving an important purpose.
A quote:
Life is an unbelievably clunky Rube Goldberg device.He talked about light regulation of the circadian cycle - I can't remember what animal it was exactly but probably fruit flies, mice or rabbits - when he kept animals in the dark (think it was actually infra-red light, which is dark to flies), they had a cycle of 22.5 hours, so every day their activity started earlier and ended earlier, whereas if they got light and dark their cycle was exactly 24 hours.
To him, a mutant is an 'entree into a problem', not just about differences between organisms. I like both ways of looking at it - mutations are interesting as differences between populations, and as ways of studying the mechanism of something.
He found that PER mRNA (from the period gene) underwent circadian oscillation and had a feedback loop (I will admit, I did not get all the details down here). Circadian rhythms affect thousands of mRNAs in each cell, with secondary and tertiary cycles and same clock in nearly every tissue - most mammalian genes are expressed rhythmically. Food metabolites seem to entrain the peripheral clocks.
Apparently fly sleep is quite similar to that of humans, and affected similarly by caffeine and ageing, among other things, making it a decent model.
Outstanding questions, according to Rosbash, are:
- why do we sleep?
- how does sleep homeostasis work? If we're sleep-deprived Monday to Friday, we sleep longer and more deeply at the weekend - what's keeping track?
- what are the rate-determing steps at the molecular level?
- how can we leverage knowledge of circadian rhythms for diseases including sleep phase disorders and diabetes?
He talked a bit about clock neurons that control sleep-wake in flies, and finished by saying that there were far too many old white dudes getting the Nobel Prize, with ages ranging from about 68 to 85, and the reason for that is the extremely fortunate environment they had during the boom in the US that this generation of scientists no longer receives. Good science rises to the top (thermodynamics), but the kinetics are uncertain, so scientists need time to do good work. He said the physicists benefitted even more from that time - the recent Nobel Laureates in Physics, the LIGO team who discovered gravitational waves, spent 50 years working on it without success, submitted the same grant renewal application every time.
He then told a couple of funny stories about the Nobel banquet, like how you're not allowed to get up during the dinner until the King gets up, i.e. for 4.5 hours. He asked the prince, who said the king basically doesn't have bodily needs, so then he joke OK, I'm gonna explain to you about diuretics. Who's gonna put one in the King's drink?
Bernard Feringa - The Future of Chemistry
Feringa got the Nobel in Chemistry recently for the design of tiny molecular machines, and his great talk focused on photopharmaceuticals and molecular motors.
He said photopharmacology involves designing the chemical structure of a drug so that it can be switched on precisely where it's needed using light, which could allow us to avoid chemotherapy side effects and mitigate antibiotic resistance. It's reminiscent of optogenetics except doesn't require genetic modifications and wouldn't be permanent - just there until the drug is metabolized and flushed out. They can also apparently switch off bacterial communication (quorum sensing), which is interesting.
'If you are in equilibrium ... then you are dead.'
The second part was about molecular motors i.e. how to design nanomaterials that can move autonomously and figure out how to control rotary motion, left and right. His team built a unidirectional rotary motor powered by light, which can cause a glass rod 10,000 times its size to turn unidirectionally too.
They mimicked the stepping motion of muscles to figure out translational motion i.e. moving from A to B, and made a nanocar as well as an artificial muscle in water that bends when lit and has a molecular weight < 1000. They even made a nanotube and added catalase and glucose oxidase to it to make a little machine that propels itself through sugar water autonomously by burning glucose. I was not expecting to enjoy the chemistry talk but it was actually seriously exciting.
Linda Partridge - The Future of Ageing
This talk was also quite interesting. Partridge said her goal isn't to make people live forever, but to compress morbidity i.e. reduce the amount of time people suffer with age-related diseases. She said longevity has increased steadily by 2.5 years per decade; Scandinavians used to live longest, now it's people in the Far East. Lifespan is only about 10% heritable; about 28% of the younger people in the room can expect to live past 100; and women live longer, but sicker. She returned to the Methuselah's Zoo idea, saying the ocean quahog clam lives for 507 years ... but then would you really want to live that long if you could only be a clam? The Dahlia anemone and hydra don't seem to age, as they're basically bags of stem cells - I wonder if the lack of specialised cells is actually the reason they aren't intelligent or specialised.
There's a C. elegans mutant (daf-2) that lives twice as long as others; it has a mutation in IGFR (insulin-like growth factor receptor), and a similar pattern is seen in mice and flies and even in humans a mutation there is associated with longevity. The animals aren't just moribund for longer, they're healthy for their extra years, with better glucose homeostasis, immune systems, motor skills, less osteoporosis, fewer cataracts, etc.
There's so much animal cruelty in most of these talks, which is upsetting. To discover that C. elegans mutant the worms were fed mutagens to see what would happen and isolate the longest-living, and they also found tha underfed rodents live longer and have better health (which makes me wonder why the rodents wanted that food in the first place - better for reproduction maybe? or just in case they didn't get more?).
Unfortunately we can't test the health effects of specific diet restriction in humans because all studies that try are destroyed by noncompliance. I have a lot of questions about this - how much diet restriction is good? How come people die of anorexia if it's good?
Diet restriction without calorie restriction can be good, and before 60ish you should have low protein (it's carcinogenic) but after 60ish you need protein to offset sarcopenia and avoid frailty. Though doesn't that increase cancer rates in an already at-risk population?
Apparently time-restricted diets are good even for genetically obese mice - they're still obese, but they're fit in terms of cardiovascular health etc.
Rapamycin extends lifespan in mice and interestingly works better in females, as well as protecting against neurodegenerative disease. (I studied this for Schols woo.) Old people respond poorly to vaccination against flu - mTORC1 inhibition (mTORC literally stands for mammalian Target Of Rapamycin Complex) improves immune response and decreases infection, potentiating the effect of vaccination. The diabetes drug metformin also targets mTORC and is currently in a clinical trial against ageing, which has just recently been recognised as a disease, though is hard to figure out treatments for because, well, when do you start giving the treatment?
Senescent cells accumulate with age because they stop being cleared by macrophages, leading to osteoarthritis; senolytics remove them, improving joint function.
She then talked about systemic factors and about experiments where they surgically joined the circulation of mice, young-young, old-old and young-old, and found that the young blood improved the health of the old mouse, which is very creepy and also so cruel. Did this hurt the mice? Why don't researchers seem to care?
In summary, four things that seem to increase longevity:
1) Suppressing nutrient signalling
2) Dealing with senescent cells
3) Systemic factors (blood)
4) Microbiome transplantation
Lydia Lynch
I'm not a fan of immunology so wasn't really looking forward to this talk. She talked about three main things: cancer immunotherapy, neuroimmunology and obesity. The cancer immunotherapy bit was very interesting and positive; she mentioned how blocking ligands that cancer cells use to calm down the immune system (CTLA and PD1) gives a huge increase in response rate in end-stage patients. Was pretty sad to see how low the survival rates were otherwise though. She said cancer immunotherapy lets us consider saying the most taboo word in oncology: cure, and that cancer immunotherapists say:
we're not trying to harness the immune system, we're trying to unleash itI definitely soured on her talk a lot after she included autism in a list of diseases and said we're looking for 'much-needed medicines to treat these diseases'.
She says a big part of the future of the field is neuroimmunology; people used to think the brain and the immune system were separate, but we've just found out they're not, so there's a lot of fertile ground there.
Finally she talked about the role of the immune system in obesity and in thermogenesis, saing that the cytokine IL-17 fuelled thermogenesis in mice and that mice lacking it all died in the cold. People laughed at that :(
She also talked about newborns doing thermogenesis using their fat cells (BAT if I recall correctly) which I saw in Lehninger when I was studying for Schols, so it was weird that it seemed to be presented as if it was new research.
Susumu Tonegawa - The Future of Learning and Memory
I wasn't really looking forward to this because I hated learning about Learning and Memory in my Behaviour module (though that module does prove useful very frequently, I must admit), but I was actually really impressed by the progress of the field - I had no idea scientists could do these things.
Firstly, he talked about how they can get mice to recall things on demand. They gave a mouse an electric shock while it was in one cage while monitoring its brain activity to look for memory engrams (biophysical changes in the brain where a memory is laid down) and then moved it to a totally different cage where it wouldn't be reminded of the shock. By stimulating the specific engram neurons they reminded the mouse and it froze, then when the light turned off it stopped freezing and so on for multiple light-on-light-off cycles.
They also gave a mouse false memories; they let it hang out in a blue box while monitoring its brain, then moved it to another box where it got a shock while stimulating the blue box memory engram neurons, then showed that it was scared of the blue box.
On the subject of false memories, apparently 75% of those incarcerated primarily on the basis of eyewitness evidence turn out to be innocent.
I do wonder whether these false memories would work for full episodic memories or just for attitudes like 'scared of this place'
They can also apparently treat mouse depressive symptoms (i.e. giving up on righting itself, anhedonia so not preferring sugar water) optogenetically?! Not sure I heard that right.
He also talked about finding serial order cells in the brain which track how many laps of a track a mouse has done; they don't measure continuous progress, but progress in discrete chunks. These cells are much more active if a reward is given every 4 laps than if every 1, and if you rotate the track the spatial code in the brain grossly remaps while the serial order cells stay basically the same, showing that the serial order and spatial codes are independent.
So yeah, that talk was a very pleasant surprise, and man how did I, a very sciencey person, not know about this stuff? This guy has done a lot. Nobel in Immunology, then he starts doing groundbreaking neuroscience.
Michael Gazzaniga - The Future of Cognitive Neuroscience
I'm pretty disgusted at this one - he came on and said his musician friend advised him to 'get on, get off, get paid', so that's what he was going to do. And that's what he did! His talk was just showing random pictures of his Caltech dorms and rambling about Schrodinger. I did tune out eventually, but in the time I was listening I certainly didn't hear anything about cognitive neuroscience. Extremely immature behaviour to be flown over and then do that - probably the biggest example of resting on your laurels (Nobelaurels?) I've seen.
Final Keynote: Christof Koch - The Future of Consciousness
I was very tired by this point and a bit annoyed by the overblown introduction Koch was given (though it was a good introduction and funny, just a bit too adoring perhaps) so I can't say I paid a massive amount of attention.
Part of it was about looking for the seat of consciousness in the brain and ruling out certain locations by the fact that you could be born without them or have lesions in them and not lack consciousness. From this he concludes that consciousness lives in the cerebral cortex.
Apparently consciousness is any experience, and that the neural correlates of consciousness are structures that maximise integrated integration. He also doesn't seem to think AI would be conscious, at least using the 'causal ability' idea, but under functionalism they would be conscious with all the attendant moral status including rights. Not assigning them consciousness conflicts with our innate desire to impute agency.
And:In your lifetime - most of the members of the audience - there will be something that thinks it's conscious, that insists it's conscious, but it's notFor a computer to have human level consciousness, it needs the causal powers of the human brain - neuromorphic architecture.
The moral status of my refrigerator is very low. If I beat my refrigerator with a hammer, that's my thing.
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