Research Blogging - Chemistry - English

Discovering underneath a “MudPit”

2012-05-24T12:17:36Z

What is referred to as “MudPit” here is not “a pit of mud” but a technique in the mass spectrometry field which stands for “multi-dimensional protein identification technology”, a very powerful approach that has been widely used since the … Continue reading →...

Washburn, M., Wolters, D., & Yates, J. (2001) Large-scale analysis of the yeast proteome via multidimensional protein identification technology. Nature Biotechnology, 19(3), 242-247. DOI: 10.1038/85686

Yang, F., Shen, Y., Camp, D., & Smith, R. (2012) High-pH reversed-phase chromatography with fraction concatenation for 2D proteomic analysis. Expert Review of Proteomics, 9(2), 129-134. DOI: 10.1586/epr.12.15

Tran, J., Zamdborg, L., Ahlf, D., Lee, J., Catherman, A., Durbin, K., Tipton, J., Vellaichamy, A., Kellie, J., Li, M.... (2011) Mapping intact protein isoforms in discovery mode using top-down proteomics. Nature, 480(7376), 254-258. DOI: 10.1038/nature10575

Clockworks: The Story of Drugs — Part 1

2012-05-24T11:15:00Z

In this installment, I will discuss why it is difficult to discover, design and develop a drug, in view of our current knowledge of physiology.With numerous, intertwined reactions happening, our body is a complex clockwork of biomachinery gears. What do you do, then, if some gears fail—that is, if you got sick? On one hand, it is a consolation that many gears are what biologists call 'redundant', which means that it's alright that a certain gear fails, because there are other gears that can take over its function. On the other hand, due to the intricacy of the gears, it is hard to pinpoint which gear is the problem, let alone fixing it. And the sheer number of gears: ICD-10 classifies tens of thousands diagnoses — tens of thousands ways the gears can fail — and those are only the ones we know; how about those we don't? Granted, some are not caused by our own gears failing, but by interferences of other, pesky gear systems: viruses, bacteria, misfolded proteins, errant microbiome, etc.; but the sense of magnitude is there.So we take drugs. In the past, the way we administer drugs is the equivalent of throwing various types of wrenches to the clockwork and then observe whether the gears are working again. Today we know more about the gears and the various shapes and teeth so that we are able to design a more sophisticated and targeted wrench, but we still don’t know enough.Our current thinking is that the machinery gears, mostly proteins, are of distinct shapes, or perhaps more fittingly, different tooth shapes. A drug has gotta fit into these various shapes. We think that if we can find 'keys' that fit to these 'locks' we can modulate that particular gear's activity: turn it up or down, switch it on or off. The key would fit into the lock, the lock would be induced to change shape / dissociate / do other curious stuff; which triggers happenings in the next gear in line. Like the dominoes falling off in line. Only that ‘the curious stuff’ may be more than a domino keeling over or a gear turning, but something that is more wackily messy, something like a Rube Goldberg contraption than a precise-looking clockwork, in this respect.How should we shape the serrated key? The first problem is scale. These gears are small — not microscopically, but nanoscopically so: To design the keys, we need the moulds, and so these very gears are the moulds. Structural biology to the rescue — X-rays crystallography/multidimensional NMR/cryo-electron microscopy can characterise the gears with varying resolutions.However, structural determination techniques face a big challenge: the interconnectedness of the system. You can't take out a gear out of context of the surrounding gears, examine it, hoping that your examinations will be valid and/or useful. Well, you sort of can. Sure, systems biology is important to gain a bird's-eye view of the whole shebang, but structural biologists routinely single out a gear and determine its structure to make it crystal-clear (heh heh) what its possible activation mechanism is, how it interacts with its activator/inhibitor, how it transduces signal to the next gear, and so on.The structural data, then, has to be taken with a grain of sodium chloride because essentially it is performed—in the physics equivalent of—in vacuo. That said, the gleaned information can be incredibly useful. Case in point: enfuvirtide. This anti-HIV-1 drug mimics a region—C-heptad repeats (CHR)—of the viral envelope glycoprotein, gp41, which is a crucial part of viral:cell membrane fusion machinery [1]. CHR is supposed to fold back to NHR like a hairpin (they are connected) and then Stuff happens, with gory details I will spare you from (Oh, fine: a channel is opened between HIV-1 membrane and that of your soon-to-be-infected T-cell; viral particles are pumped through and soon hijack your T-cell to become baby-virus-producing zombie until it bursts releasing said baby virions. Happy?) Now, the 'folding back' part is a mechanism that was uncovered through cleverly-devised experiments founded in structural studies. Thanks to this, we can deduce that if we somehow have a fake CHR, this 'folding back' can be circumvented. And that's exactly what enfuvirtide is: a dummy gear that connects to NHR gear, but not connected to the gears down the road, thus—hip hip hurray—no zombie outbreak.This is kinda cheating though. Enfuvirtide is essentially free-roaming CHR region of gp41 and no rational design work was done. For example, peptidomimetic strategy could have been used to find something similar to enfuvirtide but is able to survive the gut—since a peptidic drugs like enfuvirtide won’t, so they have to be taken intravenously. But of course, HIV-1-infected individuals don’t have the luxury of time to wait for further work on enfuvirtide optimisation.Back to the 3D protein mould model built by structural determination techniques. Ideally, we can start building up the drug à la Lego bricks, fitting the chimaera into the protein-shape mould, right, right? Couldn't be more wrong. Enter multidimensional fitting. You see, a protein ain't like your Mom's muffin pan. Besides topology, there are other dimensions to fit—electrostatic charges, hydrophilicity/hydrophobicity, to name a few. The topology is not necessarily fixedly rigid either — playing with those poppin’ stick-and-ball molecular models may give us the illusion that proteins are rigid, but protein electron clouds are more like wobbly pudding (Mmmm, pudding...); plus, different environments (pH, oxidising level) may give rise to largely different topologies (e.g. due to different protonation states, broken disulphide bridge(s), etc.).One aspect of nanoscopic scale that is somewhat entangled with multiparameter fitting is that at this scale, there is evidence that quantum effects play an important role. Several examples of such systems have been studied like photosystems and birds’ navigation, but of more interest to a medicinal chemist would be tunnelling effect in certain enzymatic reactions. Who knows if quantum effects are more routinely utilised? Our view of physiology is biasedly mechanical—even my clockwork allegory evokes the mechanistic, so a paradigm shift may well be in order as more is known about the inner workings of such systems. If you blindly design a drug that target such systems, well, you will get an entangled mess—hopefully not the quantum kind. Moving on to pharmacokinetic restrictions: the human body imposes further restrictions from the non-negotiables (e.g. a drug cannot be too insoluble otherwise how can it dissolve in the bloodstream; a drug cannot have side effects outweighing its efficacy), to convenience (e.g. a drug is preferable to be ingested rather than injected). Our own physiology thus severely restricts the chemical space of entities that make up our drug candidate pool. As I mentioned earlier, enfuvirtide is a peptide, so it won’t survive stomach acidity and peptidases in the gut. Even with intravenous administration, it would have a short half-life due to blood proteases. All peptidic drugs—insulin is one—suffer from these problems. And for drugs targeting the central nervous system (CNS), they have to overcome another obstacle, the blood brain barrier.There seems to be some sort of patterns to the drug chemical space. To wit, some have observed that certain chemical scaffolds occur more frequently than others; they are so-called privileged scaffolds (e.g. benzodiazepines) [2] and an experienced medical chemist would be able to take a look at a chemical structure and decide whether it's 'drug-like' (while an inexperienced chemist like me would only know that a drug-like molecule can't be too small and simplistic, possesses some heteroatoms, usually has an aromatic ring or two—that's about it). Problem being, at its current state, drug-likeness is an empirical measure. No one has formulated a set of rules or equations to produce a predictive model. Lipinski's Rule of Five, for example, surveys already-existing drugs and look at the prevalent drug-like characteristics. Useful as rule of thumb; hardly predictive.Next is the issue of specificity. If you choose to take a drug topically, that’s fine and dandy because you can apply the drug locally to the area in need of treatment. But if you take a drug via oral/intravenous/other numerous administration routes, the drug is going to circulate in your bloodstream. How would you ensure that your wrench would reach, and affect only, the faulty gear? You can’t—not with certainty, at least—the wrench is going to wreck another gear, and that’s why you always ha...

Eckert, D., & Kim, P. (2001) Mechanisms of Viral Membrane Fusion and Its Inhibition. Annual Review of Biochemistry, 70(1), 777-810. DOI: 10.1146/annurev.biochem.70.1.777

Welsch, M., Snyder, S., & Stockwell, B. (2010) Privileged scaffolds for library design and drug discovery. Current Opinion in Chemical Biology, 14(3), 347-361. DOI: 10.1016/j.cbpa.2010.02.018

Marusyk A, Almendro V, & Polyak K. (2012) Intra-tumour heterogeneity: a looking glass for cancer?. Nature reviews. Cancer, 12(5), 323-34. PMID: 22513401

Snakes Deceive to Get a Little Snuggle

2012-05-23T14:09:25Z

A lone red-sided garter snake. Photo by Tracy Langkilde.The red-sided garter snake is a small snake species with the largest and most northern distribution of all reptiles in North America. These northern ranges can get quite cold for any animal, let alone a reptile. Like most reptiles, they are ectotherms, meaning they regulate their body temperature largely by exchanging heat with their environment. If an animal gets almost all of its body heat from a cold environment, its body is also going to be cold… So what is a poor red-sided garter snake to do?Red-sided garter snakes that live in the northern end of their range in Manitoba, Canada spend their cold-season (6-8 months of it) hibernating in underground dens called hibernacula. Tens of thousands of snakes may share a winter den and every spring, they emerge to mate and eat and do all the other fun things that snakes do when they’re awake. (If you would like to witness the spectacular sight that is the emergence of the garter snakes, it is occurring this month in the world-famous snake-watching Interlake region of Manitoba).A whole lotta red-sided garter snakes in a spring-mating frenzy. Photo by Tracy Langkilde.When a snake first emerges from its groggy hibernation state its body is cold and movements are sluggish, which puts it at a high risk of predation from animals like crows and weasels. Females are generally at less risk of predation at this time because emergence-time is also sexy-time for this species and females generally find themselves in the middle of a writhing ball of already-warmed-up male suitors (appropriately called a mating ball). For the female, this both increases her body temperature faster (which will allow her to move faster sooner) and provides any would-be predators with many other snakes to choose from.Female red-sided garter snakes produce a male-attracting pheromone (a chemical released by an animal that affects the physiology and/or behavior of other individuals of the same species). Researchers Rocky Parker and Robert Mason at Oregon State University found that the amount of pheromone females produce increases as the females hibernate from fall to spring. This pheromone is a blend of saturated and unsaturated methyl ketones (molecules responsible for many natural odors and flavors) and males are more strongly attracted to the unsaturated components. The chemical composition of the female pheromone also changes from fall to spring, such that female spring pheromones are dominated by these highly attractive unsaturated pheromone components. Presumably, the sexier the pheromone, the more suitors are attracted and the more benefits a recently-emerged female can acquire.It seems that this smell-sexy-and-create-mating-ball strategy is a useful solution for recently-emerged females, but what about recently-emerged males? Parker and Mason collected courting male red-sided garter snakes and brought them into the lab. Then they either implanted them with estrogen (a sex hormone strongly involved in female sexual physiology and behavior) or did not (as a control group). Males with estrogen implants produced more pheromones, had higher ratios of unsaturated pheromone components to saturated pheromone components, and were more attractive to courting males. When the researchers removed the estrogen implants from some of the males, they became less attractive again. So in the lab, estrogen treatment of males makes them produce more female-like pheromones that other courting males respond to. This shows that males are capable of using this smell-sexy-and-create-mating-ball strategy, but do they use it in nature? This graph shows the amount of courtship received by females, "she-males", and "he-males" when either cold or hot. Figure from Shine, Langkilde and Mason's Behavioral Ecology and Sociobiology Paper (2012). Robert Mason at Oregon State University and Rick Shine and Tracy Langkilde at the University of Sydney, Australia collaborated to explore this relationship between temperature and male production of female-like pheromones. It turns out, male red-sided garter snakes in nature can and do produce female-like pheromones when they emerge from their den. Shine, Langkilde and Mason collected some of these males that were being courted by other males (the researchers refer to them as “she-males”). They also collected some males that were courting females (they called them “he-males”) and some females. They then exposed the snakes to different temperatures for 15-minute intervals and tested their attractiveness to other courting males. This graph shows the amount of courtship received by "she-males" when cooled (open circles) and heated (filled circles) for 15-minute intervals. Figure from Shine, Langkilde and Mason's Behavioral Ecology and Sociobiology Paper (2012). The researchers found that females were courted the most, “he-males” the least, and “she-males” were courted an intermediate amount. Interestingly, “she-males” only attracted courtship when they were cold (and their chances of survival could be improved by a mating ball) and their attractiveness shifted with every 15-minute shift in temperatures. How did they do this? 15 minutes is probably not enough time for a hormonal change to alter the pheromone composition enough to change attractiveness so drastically.An important clue comes from the composition of the pheromones themselves. Remember that red-sided garter snake pheromones are a blend of saturated and unsaturated methyl ketones and males are more strongly attracted to pheromones that have a high ratio of unsaturated components to saturated components. Well, saturated and unsaturated fats respond differently to cold: Unsaturated fats (like cooking oil) remain a liquid at cooler temperatures, whereas saturated fats (like margarine) become solid. Solids are less volatile than liquids, which makes them not smell as much. Shine, Langkilde and Mason hypothesize that the ratio of unsaturated to saturated ketones is lower in “she-males” than in females. In the cold, the high amount of saturated components of the “she-male” pheromone is turned off, which raises the ratio of unsaturated to saturated ketones, making them a...

Shine, R., Langkilde, T., & Mason, R. (2012) Facultative pheromonal mimicry in snakes: “she-males” attract courtship only when it is useful. Behavioral Ecology and Sociobiology, 66(5), 691-695. DOI: 10.1007/s00265-012-1317-4

Parker, M., & Mason, R. (2012) How to make a sexy snake: estrogen activation of female sex pheromone in male red-sided garter snakes. Journal of Experimental Biology, 215(5), 723-730. DOI: 10.1242/jeb.064923

Parker, M., & Mason, R. (2009) Low Temperature Dormancy Affects the Quantity and Quality of the Female Sexual Attractiveness Pheromone in Red-sided Garter Snakes. Journal of Chemical Ecology, 35(10), 1234-1241. DOI: 10.1007/s10886-009-9699-0

Energy Drinks: What’s the Big Deal?

2012-05-20T15:52:02Z

The sons of Red Bull are sporting record concentrations of caffeine. Are energy drinks capable of pushing some people into caffeine-induced psychotic states? Some medical researchers think so, under the right set of conditions. Red Bull, for all its iconic ferocity, is pretty tame, weighing in at approximately half a cup of coffee. Drinks like Monster Energy and Full Throttle push it up to 100-150, or the equivalent of a full cuppa joe, according to USDA figures at Talk About Coffee. That doesn’t sound so bad—unless you’re ten years old. A little caffeine might put you on task, but an overdose can leave you scattered and anxious—or worse. If you cut your teeth on Coke and Pepsi, then two or three energy drinks can delivery an order-of-magnitude overdose by comparison. Readers are entitled to ask: Are you serious? Can’t we just ignore the inevitable view-this-with-alarm development in normal kid culture, and move on? My interest began when I ran across a 2009 case report in CNS Spectrums, describing an apparent example of “caffeine-induced delusions and paranoia” in a very heavy coffee drinking farmer. “Convinced of a plot against him,” the psychologists write, “he installed surveillance cameras in his house and on his farm…. He became so preoccupied with the alleged plot that he neglected the business of the farm…. and he had his children taken from him because of unsanitary living conditions.” The patient was not known to be a drinker, reporting less than a case of beer annually. He had shown no prior history of psychotic behaviors. But for the past seven years, he had been consuming about 36 cups of coffee per day, according to his account. Take that number of cups times 125 milligrams, let’s say, for a daily total of 4500 milligrams. At that level, he should be suffering from panic and anxiety disorders, according to caffeine toxicity reports, and he would be advised to call the Poison Control Center. And that certainly seems to have been the case. “At presentation,” the authors write, “the patient reporting drinking 1 gallon of coffee/day.” On the one hand, the idea of caffeine causing a state resembling chronic psychosis is the stuff of sitcoms. On the other hand, metabolisms do vary, and the precise manner in which coffee stimulates adenosine receptors can lead to anxiety, aggression, agitation, and other conditions. Could caffeine, in an aberrant metabolism, break over into full-blown psychosis? At the Caffeine Web, where psychiatrists and toxicologists duke it out over all things caffeinated, Sidney Kay of the Institute of Legal Medicine writes: “Coffee overindulgence is overlooked many times because the bizarre symptoms may resemble and masquerade as an organic or mental disease.” Symptoms, he explains, can include "restlessness, silliness, elation, euphoria, confusion, disorientation, excitation, and even violent behavior with wild, manic screaming, kicking and biting, progressing to semi-stupor.” That doesn’t sound so good. In “Energy drinks: What is all the hype?” Mandy Rath examines the question in a recent issue of the Journal of the American Academy of Health Practitioners. Selling energy drinks to kids from 6 to 19 years old is a $3.5 billion annual industry, Rath asserts. And while “most energy drinks consumed in moderation do not pose a huge health risk,” more and more youngsters are putting away higher and higher doses of caffeine. At the level of several cans of Coke, or a few cups of strong coffee or, an energy drink or three, students can expect to experience improved reaction times, increased aerobic endurance, and less sleepiness behind the wheel. Most people can handle up to 300 mg of caffeine in a concentrated blast. Certainly a better bargain, overall, than three or four beers. But first of all, you don’t need high-priced, caffeine-packed superdrinks to achieve that effect. A milligram of caffeine is a milligram of caffeine. But wait, what about the nifty additives in Full Throttle and Monster and Rockstar? The taurine and… stuff. Taurine is an amino acid found in lots of foods. Good for you in the abstract. Manufacturers also commonly add sugar (excess calories), ginseng (at very low levels), and bitter orange (structurally similar to norepinephrine). However, the truly interesting addition is guarana, a botanical product from South America. When guarana breaks down, it’s principal byproduct is, yes, caffeine. Guarana seeds contain twice the caffeine found in coffee beans. Three to five grams of guarana provide 250 mg of caffeine. Energy drink manufacturers don’t add that caffeine to the total on the label because—oh wait, that’s right, because makers of energy drinks, unlike makers of soft drinks, don’t have to print the amount of caffeine as dietary information. And on an ounce-for-pound basis, kids are getting a lot more caffeine with the new drinks than the older, labeled ones. All of this increases the chances of caffeine intoxication. Rath writes that researchers have identified caffeine-related increases among children in hypertension, insomnia, motor tics, irritability, and headaches. Chronic caffeine intoxication results in “anxiety, emotional disturbances, and chronic abdominal pain.” Not to mention cardiac arrhythmia, seizures, and mania. So what have we learned, kids? Energy drinks are safe—if you don’t guzzle several of them in a row, or substitute them for dinner, or have diabetes, or an ulcer, or happen to be pregnant, or are suffering from heart disease or hypertension. And if you do OD on high-caffeine drinks, it will not be pleasant: Severe palpitations, panic, mania, muscle spasms, etc. Somebody might even want to take you to the emergency room. Coaches and teachers need to keep a better eye out for caffeine intoxication. Note: There is a “caffeine calculator” available at the Caffeine Awareness website, designed to determined whether you are a coffee addict. I can by no means swear to its scientific accuracy, but, based on my own, distinctly non-young person daily intake, the test told me that my consumption was likely to manifest itself as “high irritability, moodiness & personality disorders.” Can I blame it all on those endless cokes we had as kids? Growing up in the Baby Boom suburbs, we all drank carbonated caffeine beverages instead of water. Nothing much has changed except the caffeine levels. Rath, M. (2012). Energy drinks: What is all the hype? The dangers of energy drink consumption Journal of the American Academy of Nurse Practitioners, 24 (2), 70-76 DOI: 10.1111/j.1745-7599.2011.00689.x Graphics Credit: http://urlybits.com/...

Rath, M. (2012) Energy drinks: What is all the hype? The dangers of energy drink consumption. Journal of the American Academy of Nurse Practitioners, 24(2), 70-76. DOI: 10.1111/j.1745-7599.2011.00689.x

Feeling the curves of biology: How the advances in atomic force microscopy are opening new techniques to microbiology

2012-05-16T17:15:26Z

Traditional light microscopes are not able to resolve images small enough to explore the details of cells. One of the techniques used to investigate nanoscale samples is atomic force microscopy (AFM). AFM uses a very fine tip (atoms in … Continue reading →...

Fantner, G., Barbero, R., Gray, D., & Belcher, A. (2010) Kinetics of antimicrobial peptide activity measured on individual bacterial cells using high-speed atomic force microscopy. Nature Nanotechnology, 5(4), 280-285. DOI: 10.1038/nnano.2010.29

Carvalho, F., Carneiro, F., Martins, I., Assuncao-Miranda, I., Faustino, A., Pereira, R., Bozza, P., Castanho, M., Mohana-Borges, R., Da Poian, A.... (2011) Dengue Virus Capsid Protein Binding to Hepatic Lipid Droplets (LD) Is Potassium Ion Dependent and Is Mediated by LD Surface Proteins. Journal of Virology, 86(4), 2096-2108. DOI: 10.1128/JVI.06796-11

Are Invisible Extraterrestrials Out There?

2012-05-16T01:16:29Z

I recently watched The Darkest Hour, a film about invisible aliens that invade and terrorize Earth. While the movie itself leaves much to be desired, the concept of invisible aliens is one that I find noteworthy. As we search for alien lifeforms, could we be missing them due to their invisibility? While invisibility has been [...]...

Johnsen, S., & Widder, E. (1999) The Physical Basis of Transparency in Biological Tissue: Ultrastructure and the Minimization of Light Scattering. Journal of Theoretical Biology, 199(2), 181-198. DOI: 10.1006/jtbi.1999.0948

Johnsen, S. (2000) Transparent Animals. Scientific American, 282(2), 80-89. DOI: 10.1038/scientificamerican0200-80

Johnsen, S. (2001) Hidden in Plain Sight: The Ecology and Physiology of Organismal Transparency. Biological Bulletin, 201(3), 301. DOI: 10.2307/1543609

Zylinski, S., & Johnsen, S. (2011) Mesopelagic Cephalopods Switch between Transparency and Pigmentation to Optimize Camouflage in the Deep. Current Biology, 21(22), 1937-1941. DOI: 10.1016/j.cub.2011.10.014

Nikolopoulos, D. (2002) The Relationship between Anatomy and Photosynthetic Performance of Heterobaric Leaves. PLANT PHYSIOLOGY, 129(1), 235-243. DOI: 10.1104/pp.010943

Nice use of PacBio sequencing to characterize methyltransferase specificity

2012-05-12T10:34:01Z

Figure 1. Rich Roberts just pointed me to this cool paper on which he is a co-author: Characterization of DNA methyltransferase specificities using single-molecule, real-time DNA sequencing. The paper was published in Nucleic Acids Research and is from Robert's group at New England Biolabs and Jonas Korlach's and others at Pacific Biosciences. What is cool is that they used the timing of the real time DNA sequencing to identify bases in particular DNA fragments that were methylated. And this then allowed them to determine the specificity of particular methyltransferases (first tested on ones with known activity and then on ones with unknown activity). This highlights one of the unique features of PacBio sequencing - because the method watches DNA replication in real time - if something alters the timing of the replication process - this can possibly be leveraged to detect alterations in DNA chemistry (e.g., methylation, DNA damage, etc). Folks at PacBio have been promoting the methylation detection capabilities of their system for some time but I guess I did not get that interested in it because I viewed it is analogous to many other tools to quantify methylation. But with this paper I now realize that the PacBio approach (and perhaps those of other methylation detection systems) are not just about quantifying methylation status on average across a set of DNA pieces, but can also be very specific as to exactly which bases are methylated. And this in turn can be used to define specificity for a variety of unknown methyltransferases. Clark, T., Murray, I., Morgan, R., Kislyuk, A., Spittle, K., Boitano, M., Fomenkov, A., Roberts, R., & Korlach, J. (2011). Characterization of DNA methyltransferase specificities using single-molecule, real-time DNA sequencing Nucleic Acids Research, 40 (4) DOI: 10.1093/nar/gkr1146 -------- This is from the "Tree of Life Blog" of Jonathan Eisen, an evolutionary biologist and Open Access advocate at the University of California, Davis. For short updates, follow me on Twitter. --------...

Clark, T., Murray, I., Morgan, R., Kislyuk, A., Spittle, K., Boitano, M., Fomenkov, A., Roberts, R., & Korlach, J. (2011) Characterization of DNA methyltransferase specificities using single-molecule, real-time DNA sequencing. Nucleic Acids Research, 40(4). DOI: 10.1093/nar/gkr1146

The Lovelock Laboratory: A fantasy workplace in the West Country

2012-05-10T17:10:38Z

Former Mancunian James Lovelock runs the kind of a laboratory most scientists can only fantasise about working in as they grind through the humdrum bureaucracy of peer-review and never-ending grant applications. Lovelock is fortunate enough to run a completely independent, self-funded lab located in the beautiful West Country. There’s a fascinating interview with him on The Life Scientific with Jim Al-Khalili where he says lots of interesting things about elocution lessons, nuclear power, climate change and his grand theory of planet earth, Gaia....

Watson, A. (2009) Final warning from a sceptical prophet. Nature, 458(7241), 970-971. DOI: 10.1038/458970a

Life, Bit by Bit

2012-05-10T09:59:10Z

In a previous post, I’ve alluded to the issues we’re facing in defining (the conditions for) life. Also, the question of how to look for it was raised. After all, it might be substantially different from what we know. Now, … Continue reading →...

Joyce, G. (2012) Bit by Bit: The Darwinian Basis of Life. PLoS Biology, 10(5). DOI: 10.1371/journal.pbio.1001323

Of wild carrots and the death of Socrates

2012-05-08T20:04:57Z

There is a plant I keep encountering, both on foraging trips and while out running, and for a long time I had been entertaining the hope that it was wild carrot (Daucus carota), while secretly suspecting that it was actually … Continue reading →...

Schep LJ, Slaughter RJ, & Beasley DM. (2009) Nicotinic plant poisoning. Clinical toxicology (Philadelphia, Pa.), 47(8), 771-81. PMID: 19778187

Radulović N, Dorđević N, Denić M, Pinheiro MM, Fernandes PD, & Boylan F. (2012) A novel toxic alkaloid from poison hemlock (Conium maculatum L., Apiaceae): identification, synthesis and antinociceptive activity. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 50(2), 274-9. PMID: 22063758