Trying to keep both this and my new sciam blog going has been a bit of a strain. I've decided therefore that from now on all my science writing will be hosted over there, and this blog will be archived until further notice.
A while ago a conservationist called Andrew Balmford wrote a letter in Science pointing out an intriguing fact that many parents are already well aware of. Namely that while many young children are able to name and recognise over 100 species of Pokemon (fake creatures from a magical land used for a card game and now a good number of computer games) they are usually woefully ignorant of the types of birds that fly around their houses.
The Science Creative Quarterly then got the idea that if children like playing with cards of wierd and wonderful creatures why not make actual cards of real-life creatures for them to play with? Thus the phylomon project was born, and now boasts an impressive collection of cards showing diverse creatures from all over the planet.
Will it work? Well quite a few parental and teacher hopefuls have downloaded the cards, so presumably they're getting something out of it. There are rules for games, and some kids have made their own cards, but I'm not sure it will ever have quite the same appeal as pokemon. Or even dinosaurs. Dinosaurs were the original "why is my kid able to remember a hundred difficult names but can't remember what her sister's called?" item. Their fascination is that they are powerful, mysterious and almost magical. Pokemon even more so. Face it - a tree is just not as exciting as a velociraptor.
Another thing that I find harder to relate to is that while the cards do have beautiful illustrations the animals have no humanly identifiable expressions. For me, the main draw of Pokemon was that every one of the things had both a name, a load of sweet attacks, and an actual personality. The cards had expressions. Charmeleon was a sulky teanager, Bulbasaur was an overly-large slightly shy kid, Rattata was fierce and always on edge for a fight. Maybe it's just me, but I loved the fact that they each had a history, and a story and a set of almost human feelings and emotions.
So in the spirit of joining in, I have made some bacteria cards. And in the spirit of Pokemon, they all have eyes, expressions, and attacks...
They probably would have been better if I had any drawing ability. Or more than three pens.
There's the URL in all its glory, because my new blog is for Scientific American. They've recruited around thirty new people for personal blogs and there are some amazing bloggers there. Almost all of my bloggy friends have moved and there's a whole group of us that have 'graduated' from Field of Science onto this new paying gig.
So what will happen to this blog? It won't disappear! I love being here at Field of Science, so I've decided to keep it and see how that goes. Most of the proper rigorous science will go over to Sciam, and after the first few weeks of excitement pass it should be on regular twice-a-week updates. This blog has been retitled "Life of a Lab Rat" and will be more general, talking about random interesting things I've found/heard in the scientific world as I make my way through my PhD. It'll have plenty of links to the science articles I'm writing both for Sciam (and anywhere else) so people who want to read them can still keep up with them. :)
I'm looking forward to blogging at my new home, and I hope the people who stop by here occasionally will enjoy it as well!
This is the first time in ten years that I haven't had an exam around summer-time. It feels odd, everyone around me is either exam-stressed or post-exam-relaxed, it's turning to summer and there's a definite final term feeling but this time I'm not really part of it. It's been an interesting year this year, since January I've not been involved in any part of research science, other than writing about it.
However luckily I'm still surrounded by lectures, seminars, talks and various other interesting stuff which no one seems to mind me occasionally turning up too. Seeing as I haven't written much about virus's lately I headed over to a talk the other day about Marek's disease, which is caused by a Herpes Virus and has a rather devastating affect on chickens.
It makes them stand like this :(
It started back in the sixties, when rather a lot of chickens suddenly started dropping dead, sometimes up to 50% of all the stock in a large barn. Bear in mind these weren't the happy pecking-around-shrubs-of-grass chickens that feature on the front of free-range eggs, but rather a lot of chickens quite closely packed inside a big barn. The cause was found to be MDV - Marek's disease virus. After a lot of work a vaccination was found and given to all the chickens. Over $2 billion was saved by this, and the chickens were able to survive, right up until they got slaughtered for food.
But then, around the 1980s the disease suddenly reared it's head again, this time in a far more virulent form imaginatively labelled vvMDV (which stands for very virulent MDV). More research, another vaccine, and the deaths stopped.
Until just before 2000 when the virus evolved again into an even more virulent strain called vv+MDC, which means exactly what you think it does. Another vaccine was made (called Rispens) but at this point it was becoming fairly clear that this virus was behaving oddly. Three times it had changed, becoming more and more deadly each time:
Image from the presentation slides showing the development of new strains with an increase in virulence.
This is not normal behaviour. Virus's rely on their hosts, they can't replicate, survive or do anything without a host cell, which means they have a vested interest in keeping the host alive. If anything, viral strains should evolve to become less virulent; a virus that kills the host will be a virus without a host and is therefore less likely to survive and propagate than a virus with a host.
It turns out in this case that the evolution of increase virulence is down exclusively to the way the vaccine interacts with the virus. The virus works by being inhaled into the chickens lungs, getting into the cells of the immune system (B and T cells) and causing a latent infection of the lymphocytes (T cells). Virus cells can also work their way to the epithelial cell of the feather follicles and will shed from under the feathers, thus keeping the virus in circulation.
In an ideal situation a vaccine would produce what is known as "sterilising immunity", where use of the vaccine kills all viruses dead. This is how almost all human vaccines work. With the Marek's disease vaccine however, the virus was not killed completely, but could still replicate and shed from the feathers. This means that the virus was still within the system, able to change and evolve. The vaccine however, does make the virus less likely to spread, which means that a more virulent form that the vaccine does not protect against is able to outcompete the less virulent strain. Because the chickens are all in very close proximity, and because there are a lot of them, the more virulent strain can spread much faster throughout the population. With normal chickens, in small isolated populations this would not happen as a virus that virulent would run out of host and die out.
This creates a paradox - vaccines are needed to stop the chickens getting the virus, but at the same time use of the vaccine is creating an evolutionary environment in which a more virulent virus can grow. There are some responses to avoid this though. Firstly, to develop a virus that produces sterilising immunity, i.e that kills all thee virus dead. Secondly, to allow the chickens more room and freedom to stop the virulent strains spreading so quickly. And while this second solution sounds like every animal-rights campaigner's dream, remember that it only really works if very few people in the world eat chicken. In reality there are lots of people, and a limited space for chickens - eating chickens which have lead a happy healthy life is a privilege for a few, not the reality for the majority.
--- Witter RL (2001). Protective efficacy of Marek's disease vaccines. Current topics in microbiology and immunology, 255, 57-90 PMID: 11217428
Witter RL (1997). Increased virulence of Marek's disease virus field isolates. Avian diseases, 41 (1), 149-63 PMID: 9087332 ---
In posts one and two of this mini-series I explored how plants can defend against bacteria by releasing dangerous chemicals and by killing off cells. This post looks at how surviving one bacterial attack can make plants more able to survive subsequent ones with both local and systemic acquired resistance.
Locally acquired resistance is the simplest to manage, and provides a clear advantage. If cells have been attacked once it makes sense to defend them in case of a second attack. Plants achieve this by strengthening the cell walls in cells that have survived the bacterial attack. Experiments adding elicitors (bits of bacteria that stimulate the plant pathogen receptors) to plant cells showed that proteins in the cell wall became oxidatively cross-linked as they sense the bacteria. Interestingly the molecule responsible for this is hydrogen peroxide, one of the molecules also involved in the cell-death response discussed in post two. If it doesn't kill the plant, it makes it stronger.
The cell membrane is the blue box at the bottom, whereas the cell wall is the light blue rods in the middle. It is the cell wall which is strengthened. Image from wikimedia commons.
This response is all very well for plant cells which happened to be near the site of infection, but what about the rest of the plant? Is it possible for cells on the other side of the plant to be warned and ready for a pathogen attack? Despite the inability of plant cells to move, the answer surprisingly is yes. Cells at the site of infection can release a chemical called salicylic acid which moves through the plants vascular system (the system which also delivers sugars and other important nutrients to all parts of the plant).
The chemical structure of salicylic acid, which is chemically similar to the active component of aspirin.
Following an infection, the levels of salicylic acid were found to rise dramatically in cells around the zone of infection, before spreading through the rest of the plant. This isn't a species specific response either but one found in many different species; grafting parts of one plant onto another did not stop either plant from acquiring resistance. In response to the salicylic acid signal cells start accumulating small amounts of hydrogen peroxide, which can lead to the same cell wall strengthening seen around the area of infection.
As well as salicylic acid it has also been suggested that infected areas of the plant can release the volatile molecule methyl salicylate, commercially known as oil of wintergreen. Rather than travelling through the plant this signal is airborne, allowing transmission not just to other parts of the plant, but to neighbouring (and therefore likely to be related) plants as well. As the only difference between these two signalling molecules is the addition of a small CH3 group, the methyl salicylate can easily be converted back into salicylic acid once it reaches the cells where it can cause the same downstream response.
If anyone was wondering quite why I've suddenly been into plants part of the reason is that the BBC is showing a program called "Botany - a blooming history" and I've been catching the episodes. Despite the slight naffness of the title, it's actually a really good program showcasing experiments, personalities, and the scientific method as it unfolds the history of plant science. You can catch the episodes here on iPlayer.
--- Brisson, L., Tenhaken, R., & Lamb, C. (1994). Function of Oxidative Cross-Linking of Cell Wall Structural Proteins in Plant Disease Resistance The Plant Cell, 6 (12) DOI: 10.2307/3869902
The first post of this mini-series covered how plants can defend themselves against bacterial attack by releasing chemicals, either on a regular basis or as a specific response to the attack. This post will explore the hypersensitive response, which allows plants to rapidly kill of cells around the area of infection, starving the bacteria of nutrients to prevent it spreading. The end result is a small area of dead plant matter, with the rest of the organism unaffected.
One of the main differences between plants and animals that I flagged up in the last post is that plant cells don't move. The use of the hypersensitive response shows another; plants have a very non-determinant structure. Animals will grow towards a clear well defined shape and once they get it, they stick with it. Your body does change as you grow older, but it's not about to grow an extra leg. Plants on the other hand may have determinant structures within them, such as leaves or flowers, but the overall organism can just keep growing for as long as it needs to. If a leaf is lost through disease, the plant can just grow a new one, or several new ones.
Because of its non-determinant nature it is a lot easier for the plant to kill parts of itself off in order to stop an infection spreading. One way that the hypersensitive response does this is by the production of large numbers of reactive oxygen species in cells surrounding the site of infection. These include hydrogen peroxide, and various hydroxide and oxygen containing free radicals. Free radicals are species with one unpaired electron and therefore are extremely reactive and extremely dangerous. These free radicals lead to chain reactions that can break down lipids in the membrane, inactivate enzymes and generally roll around like a loose canon causing havoc within the cell.
As well as reactive oxygen species, the cell also experiences large ion fluxes, as potassium and hydroxide ions flood into the cell and hydrogen and calcium ions flood out. These result in the cell releasing any stored toxic compounds it might have (which may also help to kill the bacteria) and may serve to integrate the mitochondria into the process of cell death (see reference one). As mitochondria are crucial in coordinating the programmed cell death of animal cells it would be surprising if they did not play some part in the controlled destruction of plant cells. The actual sequence of destruction varies from plant to plant, but the overall result is the same, and area of dead plant tissue within the still healthy surviving plant.
A leaf infected with tobacco mosaic virus, showing lighter areas of dead leaf interspersed with the green areas of normal growth. Image from wikimedia commons.
The plant hypersensitivity response can (if you want it to) be considered analogous to the human innate immune response, in that it occurs directly in response to a bacterial attack, and it occurs only at the site of bacterial infection. Plants, however, also have ways of making more long-term changes to protect against bacterial attacks in the future both at the site of the old reaction and throughout the whole plant. How the plant achieves this, without any cellular movement, will be the topic of the final post in this mini-series.
--- Lam, E., Kato, N., & Lawton, M. (2001). Programmed cell death, mitochondria and the plant hypersensitive response Nature, 411 (6839), 848-853 DOI: 10.1038/35081184
Pontier, D., Balagué, C., & Roby, D. (1998). The hypersensitive response. A programmed cell death associated with plant resistance Comptes Rendus de l'Académie des Sciences - Series III - Sciences de la Vie, 321 (9), 721-734 DOI: 10.1016/S0764-4469(98)80013-9
Taiz, Zeiger, Plant Physiology, third edition Sinauer Associates 2002. ---
Although I've never officially studied immunology, my second year course in Pathology left me with a pretty solid idea of how humans defend themselves against bacterial attack. Even without a university course I've always been vaguely aware of the presence of immune cells; the B and T cells that make up the adaptive immune system, the clotting response, and the symptoms of inflammation around the site of infection.
How plants responded to bacterial attack was still a complete mystery though. One of the main things that distinguishes plants from animals is that animal cells are a lot more motile, they can move through the body. Animal cell movement is crucial during the development of the embryo and even once the body is fully formed cells still rush around the blood stream and slide around in the epithelial layers. The correct functioning of the immune system relies on cells being able to do this, dendritic cells and macrophages will pick up bits of bacteria at the site of infection and go running back with them to the lymph nodes which will start organising the best way to deal with the infection.
A macrophage in the lungs, from Wikimedia commons. The macrophage engulfs bacteria and eats them, which requires it to be able to move.
With a few odd exceptions plant cells do not move. Not at all. There is no movement of cells during the seed development, and even the movement of plants towards sources of light and water is caused by cells growing rather than moving. How then does the plant respond and react to bacterial infections?
There are several different ways, which is why this is a three-part post series:
Part One: Deadly Chemicals
One of the simpler ways to remove a bacterial infection is to release a chemical that is harmful to the bacteria. There are quite a lot of plants that produce antibacterial products as normal secondary metabolites, an example of which is saponins, a group of compounds which have soap-like properties. As saponins are lipid soluble they can break up bacterial membranes by binding to sterol compounds within the membrane and disrupting the structure. Studies done on oats (reference one) have shown that reducing the natural levels of saponin made the oat plants much more vulnerable to fungal infections.
Rather more excitingly, plants can also release certain chemicals in response to a bacterial attack. When bacteria attack plants have been shown to release an assortment of hydrolytic enzymes - glucanases, chitinases, etc that break down cell walls and membranes. These are known as pathogenesis-related proteins as they are specific to bacterial or fungal attack. One of the better researched is a group of chemicals called phytoalexins. In normal conditions neither the phytoalexins themselves, nor the enzymes used to make them, are found within plant cells. It is only after a microbial invasion that the enzymes are transcribed and translated and the phytoalexins synthesised.
In order to respond specifically to bacterial attack, the plant needs to be able to recognise bacteria as invading elements. Like many animals, plants have what are known as "Toll-like receptors" that recognise bacterial pathogen molecules (which in animals are referred to as PAMPS Pathogen-Associated Molecular Patterns but in plants seem to be called elictors) such as bits of protein and polysaccharide fragments from the bacterial cell wall. [EDIT - I have since been informed that PAMP is used quite widely among plantscis now as well]
Comparison of the plant and animal TOLL receptors. The blue and red lines are the receptors, and the blobs attached to them are the bits of pathogen. The yellow boxes labelled PK stand for 'protein kinase cascade' which carries the message through the cell to turn on the genes required. Diagram adapted from reference two.
By recognising pathogens as they invade, the plant cells can launch a deadly chemical attack against them, without requiring any movement. None of this requires the cells to travel around, and until the bacteria develop resistance to the chemicals being used, it can be highly affective. Chemical warfare however, is only one of the strategies that plant cells can adopt to protect themselves against invading microorganisms, and my next post will cover the second - depriving the bacteria of valuable nutrients by committing cellular suicide.
--- 1) Papadopoulou, K. (1999). Compromised disease resistance in saponin-deficient plants Proceedings of the National Academy of Sciences, 96 (22), 12923-12928 DOI: 10.1073/pnas.96.22.12923
2) Nürnberger, T., & Scheel, D. (2001). Signal transmission in the plant immune response Trends in Plant Science, 6 (8), 372-379 DOI: 10.1016/S1360-1385(01)02019-2
3) Taiz, Zeiger, Plant Physiology, third edition Sinauer Associates 2002.
It's been in the news a lot, but for those who've missed it there's a particularly deadly strain of E. coli that has reared its head in Germany. The source of the bacteria is not yet known although both cucumbers and beansprouts have been blamed, and German authorities are advising people to stay away from raw leafy vegetables. Vegetables don't usually harbour their own strains of E. coli, but the thought is that animal manure (which most definitely does contain E. coli) used to fertilise the vegetables may be carrying the deadly strain.
This plate is more deadly than you can possibly imagine
I talk about E. coli a lot in my blog as I use it for most of my experiments. The strain I use is called K12 and is completely harmless to humans. It's also used in sterile conditions and not allowed to leave the lab. The strain that's causing panic in Germany is called O104:H4 which is an enterohemorrhagic strain which can cause bloody diarrhoea and also attack the kidneys. Working from news sources (as there don't seem to be any papers out yet!) it seems to have picked up the DNA with a kidney damaging toxin as well as having proteins that help it to stick strongly to the intestinal cell wall. Other bloggers have looked at this in more exact detail (and shared their findings, which is pretty awesome), including which parts of the DNA have changed in this new strain.
The labelling isn't just arbitrary either, it tells you exactly what antigens the bacteria is carrying, and antigens are the things that the immune system recognises to help your body attack the disease. There are three different types of antigens in the E. coli species; O (in the new deadly strain), H and K (in my lab strain). The letter and number after the : mark "O104:H4" refers to the flagella antigen. Strains which share the same antigen types will have similar patterns of virulence.
As well as trying to understand the genetic code and how this strain differs from other deadly and non-deadly E. coli, scientists are also trying to find exactly where the bacteria are coming from, testing vegetable sources in an attempt to isolate it. Both cucumbers and beansprouts have now been tested for the strain isolated from patients, and both have shown negative results.
Understanding where the deadly strain arises from is less useful in terms of the scientific investigation, but crucial for stopping the disease from spreading, and helping to understand how to avoid such strains developing in the future.
If you're worried about the vegetables you're eating then the best advice I can give is to cook before eating. E. coli are not able to withstand the high temperatures of cooking and unlike bacteria such as clostridium they do not release toxins onto the food. Clostidium produce exotoxins directly onto your food whereas E. coli produce endotoxins once they get into the body. For the more sciencey minded, it's Gram positive bacteria which tend to produce exotoxins, whereas Gram negatives produce the endotoxins.
It's only once the E. coli enter your body that they start producing 'toxins' and these toxins are usually parts of the bacteria as they are broken down by the immune system. If you manage to destroy the bacteria before eating the food, then it will be pretty much safe to consume. Note that this technique does not work for exotoxins, which are actively secreted by the bacteria (Gram positives like secreting things) onto food before you eat it.
Studying bacteria does sometimes feel like a little niche set slightly apart from the real world, which is full of lumbering eukaryotes making complex non-rational interactions. News like this an interesting reminded that bacteria don't just affect health, but also have strong economic and political implications. Spanish cucumber salesmen are trying to sue Germany, Russia's getting all smug about EU health regulations, and German tourism is being affected. All because of E. coli.
This is the eleventh edition of the Carnival of Molecular Biology, a travelling goodie-bag dealing with all things small and cellular. When this carnival was first started up I must admit I had more of a hope than a certainty that enough people would be interested in the world of the small and cellular for it to continue, but we've passed the tenth edition, and it's still here!
Long may it remain
For this edition, we'll start off with the all important question, what actually is a biochemist? And is it significantly different to a chemical biologist? My reasoning on this is clear; a biochemist is a biologist who likes the chemical side of things, and a chemical biologist is a chemist who is fascinated with biology. They both may work in the same lab, but will have different training backgrounds and different ways of seeing the world. Chris Dieni gives a more thorough explanation of this over at BenchFly.
Science works by experiment, which is why I'm happy that we have two posts this carnival covering experimental techniques used to explore the intracellular landscape. The Biotechnology blog takes us through the technique of 3-dimensional cellular arrays which build up a picture of the entire cell, rather than just using thin slices through the cell. Psi Wavefunction goes deeper and looks at how to study the DNA within cells, and as she works with protists, it's some very strange DNA indeed.
Lineup of DNA, from Psi's post
As well as biologists and chemists, engineers tend to get involved in this molecular-biology gig and when they do they almost inevitably start talking about lego. Lucas from Thoughtomics shows us how life can be thought of as lego blocks, and how planets with life on them could potentially be found, even if the life is not as we know it.
Back in the realm of pure biochemistry is a brilliant post from It Takes 30 which explores how one pathway within the cell can lead to many different outcomes. It focusses on the pathways of p53, an unassuming little molecule that is one of the most important within the cell, as it responds to cellular DNA damage.
From the It Takes 30 post - a diagram many biochemists
are familiar with!
Finally, we'll finish with a last post from Psi, which is part of a multi-post essay about constructive neutral evolution and is well worth reading. As someone who only dashes of quick little posts, it's great to read a well researched longer post, which goes into a good (and accessible!) coverage of an important topic.
That's all for this edition! If you want to get involved (and I strongly recommend it, carnivals are interesting, great publicity, and also quite fun) submit any molecular-biology related posts here. The next edition will be at PHASED and the more posts it has, the bigger and better the carnival will be.
For those of you who might have missed my writing, I've written a piece for the Varsity magazine "Not-Sci" section, which examines false scientific claims. My piece is looking at a little Gadget called Totem Confidence, which claims through the power of a CD and a keyring to increase confidence, reduce stress, and reduce your bank balance by £14.97. You can read it here. LINK IS NOW UP AND RUNNING AGAIN.
For those of you who want to promote your own work, or have a desire to read all sorts of other pieces, Lab Rat will be hosting the MolBio Carnival on the 6th. If you've written (or read!) any blog posts that deal with the inner life of the cell then please do submit them it would be great to have loads of interesting posts.
And after that ... the science posting will return with a vengeance, because I have a PhD starting up in a few months, and I want to be a microbiological expert before I head in!
So, it's been a little quiet around here for the last week or so. Mainly because I went from the state of having a PhD application sliding it's way slowly around the Gormenghastian admissions system to suddenly having a PhD conformation and a funding application deadline in very close succession. I spent last weekend frantically turning what was a 200 word project summary into both a 100 word abstract and a 1000 word project proposal.
Also A-level time is right on top of us, which means that tuitions momentarily went slightly haywire out of student panic. I now know the A-level chemistry course back-to-front, which is a bonus as I'd sort of forgotten bits of it during the course of my degree.
Anyway, the exciting news is yes I do now have a PhD lined up for next year! I have one years funding, and am trying to look for creative ways to turn it into three years funding. Naturally I am insanely excited about starting the PhD, and getting back into a lab. One thing I'll have to do is get all up to scratch on the reading list, having been out of the science scene a bit since January. Reading papers to me means blogging about papers, so stay tuned for a deluge of information about How Antibiotics Are Made along with the occasional interest paper about This Awesome Thing I've Found Bacteria Do.
And if you are neither interested nor excited in antibiotics then prepared to be deluged with me telling you why you should be :p
This is the 35th edition of the Carnival of Evolution, and I'm very excited to be hosting it here at Lab Rat. I love blog carnivals, I think they're a great way to share work and read up on all the people writing about a topic you love. Each carnival tends to bring up interesting posts by 'regulars' as well as random newbees, all with something fascinating to say.
Whats I find really interesting about the science of evolution is that it brings together so many people from different fields of study. Understanding and studying the common origins of species, and their diversification requires skills that range across multiple different types of science, so in this carnival I am going to celebrate the multidisciplinary nature of the study of evolution.
Evolution isn't just about fieldwork, there's also an appreciable amount of systems modelling involved, which requires computer competency. BytesizeBio goes through the creation of the "Methinks it is like a weasel" program, in a special celebration of Shakespeare's birthday.
There's a bit of an overlap between these and the microbiologists, but we have one definitely medical post from Genome Engineering, as to whether there might be a genetic and evolutionary component driving an increase in premature births.
The Archaeologists and Anthropologists
I am never totally sure about the true difference between Arch and Anth, all I know is that they both get very annoyed if you mistake them for the other one. So in the interests of human unity I've put them together. The Mermaid's Tale brings us another great post exploring the concept (and the movie!) of Deep Time, and how deep time in human evolution can be portrayed. Evolving Thoughts brings us further updates on whether BRIAN BLESSED can (or even should) be considered a monkey or an ape. There's also some further discussion of the Piltdown man from Genome Engineering.
The Social and Political Scientists
Evolution has never been just a matter for research scientists. Whether this is a good or bad matter is up for debate, but it cannot be ignored that there is a political dimension to the applications and even the teaching of evolution. At Political Descent there's a post on the teaching of evolution in classrooms - some of the historical reasons held by both camps might surprise you. Evolving Thoughts looks at the recent attitudes held by the pope, and attacks the belief that evolution is a "random" process. Finally, there's a lovely lyrical piece by e.m. cadwaladr with thoughts on seeing the statue of Martha, the last passenger pigeon in the USA.
That brings us to the end of this carnival edition. The next one will be the same time next month;go here to submit your posts and see how many more scientific fields we can cover in the study of evolution.
The social behaviour of bacteria is something that I get very excited about. From the wolf-pack hunting strategies of Myxococcus xanthusto the terminal differentiation of cyanobacteria, it's something that I never get tired of writing about. As well as providing interesting quirks of bacterial behaviour, living within a colony also gives new scope for exploring the evolution of bacteria; not just as single entities but as a fully functioning social group.
One of the differences of living within a social colony as opposed to alone means that altruistic-type behaviour has to be adopted. Bacteria living within a biofilm need to excrete the sticky goo that holds the biofilm together, which is problematic because synthesising and secreting goo takes up a lot of energy. So within this colony, there will be 'cheaters' - those bacteria that live in the surrounding goo produced by others, while making none themselves.
A bacterial biofilm, showing individual bacteria in green. Image taken from the FEI website, shown there courtesy of Paul Gunning, Smith & Nephew
As with all colonies, cheating might benefit the individual but has no benefit for the colony as a whole. Too many cheaters and there won't be any biofilm. And recently an even more subtle form of cheating has been shown within the biofilms of the bacteria Pseudomonas aeruginosa, with bacteria that don't just refuse to make vital sticky chemicals, but also abstain from the entire process of forming a biofilm.
Bacteria use a complex communication system called quorum sensing in order to determine how many other bacteria they are surrounded by. Once enough bacteria are present, all signalling their existence, the biofilm will start to form. However some bacteria isolated from the biofilm were shown not to be taking part in any quorum sensing at all. Quorum sensing appears to be quite a burden for a growing cell - cells with the quorum sensing genes knocked out tend to grow a lot faster that the socially conscious cells that allow biofilms to form.
The paper that goes through this (reference one) highlights it as a form of social cheating, with bacteria avoiding quorum sensing to benefit themselves while mooching off the quorum sensing behaviour of others. I'm not entirely certain that this is the case though. It may just be an good example of job allocation within the bacterial society. Clearly not all bacteria are required to be continually quorum sensing, so why should they all have to? Would it not be more sensible to have some exempt from that task, so that they can concentrate on growing, dividing, and spreading the colony? This may be more a case of tax-breaks than of benefit-cheats.
Social evolution doesn't just take place within species, but also between them, and like every other organism bacteria are in a constant state of coevolution with both their 'prey' and their predators. Most predator-prey interactions take long periods of time to study, but the beauty of bacteria is that you can go through several generations in the course of one week's growth. Studies of the bacteria Pseudomonas fluorescens and its bacteriophage parasite showed that both the bacteria and the bacteriophage evolved far quicker when interacting together than they did when competing against a non-changing opponent.
'Evolve' here means that the bacteria and the bacteriophage showed a greater change in their genetic makeup, and a greater genetic divergence from bacteria not pitted against the phages. Unsurprisingly, the genes that changed the most were those involved in host-phage interaction. This study (reference 2) is also a great example of the usefulness of whole genome sequencing. Whole populations of bacteria and phage were allowed to evolve both together and separately and then just sent away for sequencing with the results analysed at the end.
You really can't be an anti-evolutionist while studying bacteria. They just do it so damn quickly and often you can see it happening.
Sandoz, K., Mitzimberg, S., & Schuster, M. (2007). From the Cover: Social cheating in Pseudomonas aeruginosa quorum sensing Proceedings of the National Academy of Sciences, 104 (40), 15876-15881 DOI: 10.1073/pnas.0705653104
Paterson S, Vogwill T, Buckling A, Benmayor R, Spiers AJ, Thomson NR, Quail M, Smith F, Walker D, Libberton B, Fenton A, Hall N, & Brockhurst MA (2010). Antagonistic coevolution accelerates molecular evolution. Nature, 464 (7286), 275-8 PMID: 20182425
In one weeks time, the Carnival of Evolution is coming to Lab Rat! Like most of the bloggy carnivals floating around, it's a travelling one and I am very excited to be hosting it.
If you're a blog reader, I hope you'll enjoy looking through a variety of posts from a couple of different people, all on the topic of evolution. If you're a bloggy writer then write me a post! Blog carnivals are a great way to get your blog noticed, and to get more exposure for your writing. Also it's fun to read other people's thoughts on a topic as well as sharing your own.
You can submit articles and blog-posts here. There's still one week left, so plenty of time to get a nice post written!
[And I am aware that the SGM series is going a little slower this time around. I'm really enjoying doing it and I will get through it, I'm just taking my time, as there's a lot of other stuff going on in my life at the moment.]
One of the first topics that I learnt in Biology was that there are two types of things; living things, and dead things. Living things are given a whole host of distinguishing characteristics (growth, reproduction and, my favourite, irritability) where as dead things are defined as everything else. Biology was usually defined as the study of living things.
As I grew older, I found that there were many complications to this neat little classification. Viruses - which are neither fully living, nor properly dead. A whole organism can be dead, despite the fact that many of its cells are still alive (how alive is a freshly killed animal? Or the flowers in a vase?). And of course what is for me the most intriguing case, that of dormant bacteria.
Dormancy is an odd state to be in. A dormant organism shows none of the signs of being alive. It does not eat, grow or divide (although some very basic metabolic processes may still continue). It shows no response to any outside stimulus, and can often be placed in conditions that would
lead the living organism to perish, such as extremes of temperature and pressure. Yet somehow just one simple stimulus can cause this previously dead looking organism to spring magically back into life.
Bacteria are not the only things that can go dormant. Some
animals can as well, the most famous example being tardigrades -the thing shown on the right that looks a bit like a plushie made by Tim Burton (image from wikimedia commons). Yeast are well-known for forming dormant spores, and it can be argued that a seed is technically a dormant plant, just waiting for water to be added to bring it back to life.
One of the most medically important dormant bacteria is Mycobacterium tuberculosis which infects humans and leads to TB. One of the reasons for its pathogenicity is that they can go dormant, both outside the body (which makes them hard to shift from a hospital) and inside the body, after the primary infection (which makes them even harder to shift from inside a human body).
Although the latent cells can remain within the body for many years, sometimes never coming back from dormancy at all, ideally there should be some signal to bring them back to life. These signals are known as "resuscitation-promoting factors" or RFPs. These RFPs are required for virulence, and to bring the bacteria back from dormancy, but are not necessary for the growth and proliferation of cultures in the lab.
Within human tissues, and throughout the cycle of the disease, you can track these RFPs to try and get an insight into what the bacteria is up too, and when it may move from latent periods to periods of active growth. As well as being useful for tracking the course of infection, this might also have therapeutic implications. If you can convince the bacteria not to come out of dormancy then you have an infection state that might not be completely curable but is at least controllable.
How organisms survive in a state of dormancy, and indeed how they ever come out of it, is a subject I find really fascinating. I'm unlikely to ever get to do much research on it (because as fascinating as it might be screwing around with my little bugs till they do what I want is endlessly more fun) but I'll probably have a good few more posts writing about it and exploring how it works.
Kana BD, Gordhan BG, Downing KJ, Sung N, Vostroktunova G, Machowski EE, Tsenova L, Young M, Kaprelyants A, Kaplan G, & Mizrahi V (2008). The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Molecular microbiology, 67 (3), 672-84 PMID: 18186793
Davies AP, Dhillon AP, Young M, Henderson B, McHugh TD, & Gillespie SH (2008). Resuscitation-promoting factors are expressed in Mycobacterium tuberculosis-infected human tissue. Tuberculosis (Edinburgh, Scotland), 88 (5), 462-8 PMID: 18440866
It's a pretty well known fact now that the human body contains lots of bacteria. Bacteria live on your skin and in your throat and gut, for the most part completely harmlessly, protecting your body from more dangerous invaders.
But something that doesn't get mentioned quite so often is that humans are not the only animals with a corresponding posse of bacteria. Other animals have them as well, including insects. From a bacterial point of view both your body and an insect's body are merely new lands to be colonised, and if they can colonise those lands without totally destroying them, then so much the better.
Like human bacteria, some bacteria that live within insencts have formed a symbiotic relationship, where the insect relies on the bacteria for survival. The pea aphid (shown to the right - photo by Marlin E. Rice) contains a symbiotic bacteria, Buchnera aphidicola that is required to produce one of the major amino-acids used to make important proteins. Completely sequencing the genome of the aphid shows that it does not contain the gene for argenine; it requires the Buchnera to make it. Likewise the sequenced bacterial genome lacks the genes for animo-acid deregulation, and several other minor amino acids. It gets these from its insect host. The bacteria lives within the host, in specialised little cells, and is passed down from mother aphid to daughter as without it the aphids will not survive.
This raises important questions about the control of the genetic activity of both the bacteria and the insect. If the insect needs more argenine, it must have a way of telling the bacterial genome to produce it, likewise if the bacteria requires more of the non-essential amino-acids it needs to be able to push the insect to make them. Modeling flux pathways for the creation and degredation of some of these amino acids helps to build up a picture of how this control can function, at a metabolic level if not a genomic one. The flux analysis also shows how important this symbiotic relationship is, for both the bacteria and the insects.
Leaf cutter ants (shown on the left - image from Wikimedia commons) have what is possibly the most complex and fascinating of interactions with microorganisms. For a start, they harvest fungi growing it in little gardens and feeding it with mashed up plants. This fungi can be susceptible to infections, so the ants also need to provide pesticides to keep their crops alive. As ants have not quite reached the level of large scale chemical manufacture, they have to rely on symbiotic bacteria to produce the antibacterial and antifungal compounds they need. The bacteria they use are species of Pseudonocardia and Streptomyces which produce a large number of secondary metabolites that can be used to destroy the fungal-infectors. The ants excrete these secondary metabolites in their waste, which can then be moved into the fungal garden. The bacteria also showed some anti-fungal activity against the fungus growing in the gardens, so could be used to control how far the crop spreads.
I'm always wary of ants, I certainly got bitten by them enough times as a kid. With their little societies and gardens and wars and multistory-housing compexes they are scarily human for a tiny piece of exoskeleton with legs.
--- Wilson AC, Ashton PD, Calevro F, Charles H, Colella S, Febvay G, Jander G, Kushlan PF, Macdonald SJ, Schwartz JF, Thomas GH, & Douglas AE (2010). Genomic insight into the amino acid relations of the pea aphid, Acyrthosiphon pisum, with its symbiotic bacterium Buchnera aphidicola. Insect molecular biology, 19 Suppl 2, 249-58 PMID: 20482655
Thomas GH, Zucker J, Macdonald SJ, Sorokin A, Goryanin I, & Douglas AE (2009). A fragile metabolic network adapted for cooperation in the symbiotic bacterium Buchnera aphidicola. BMC systems biology, 3 PMID: 19232131
Schoenian I, Spiteller M, Ghaste M, Wirth R, Herz H, & Spiteller D (2011). Chemical basis of the synergism and antagonism in microbial communities in the nests of leaf-cutting ants. Proceedings of the National Academy of Sciences of the United States of America, 108 (5), 1955-60 PMID: 21245311
This is the first of the Spring 2011 SGM series; where I steal random topics from the Society for General Microbiology Spring Conference and write about them in my blog. It should be noted that I am in no way affiliated to the Society, I'm just currently not rich or scientific enough to go to their conferences. (next year...)
I was quite intrigued when I saw this topic, as microbial diversity has always seemed to me to be a little bit like rats. Interesting to the people that study them, irritating and potentially hazardous to those who don't, but not really in need of any special protection. Bacteria evolve quickly, and share DNA easily, forming many, many diverse species capable of occupying a wide variety of niches.
However while bacteria are indeed very diverse and happy to remain so, the challenge comes in cataloguing all of that diversity. New bacteria need to be examined, named, placed in a taxonomic group, and preferably stored so that if anyone has a particular urge to work on (say) a specific type of hydrogen-eating swamp bacteria, they can find a sample of it and do that work.
What I hadn't realised was that there are quite a few places that are designed to store bacterial cultures. One such place is the DSMZ collection in Germany which boasts over 20,000 cultures of assorted microorganisms. These are stored as dried samples, not alive yet easily able to resuscitate. For a small fee, you can order a sample from them, together with instructions as to how to bring it back to life and culture it within a laboratory. Without storage facilities such as these, it's easy to see how interesting new bacteria would simply get lost, due to freezer melt-downs in labs, or people discarding the wrong samples.
It's not just the finding and the storing of bacteria that are vital in order to maintain scientific knowledge of their diversity, you've also got to name the things. After all, an unlabelled catalogue is no use at all. And with the name comes characterisation - a whole list of the properties and behaviour of the bacteria down to as much biochemical information as is feasible. The speed and accuracy of full-genome sequencing does make this a lot easier, but there are still many properties that depend on more than just the genes. A bacterium might possess the gene for (say) iron metabolism, but that doesn't mean it uses it all the time, or indeed at all. Knowing the genome sequence also makes it a lot easier to quickly place a bacterium into an existing group or species. Although bacteria do share DNA between each other, recently acquired DNA can usually be distinguished from the core genes that mark the species.
UK strains can be acquired through the Health Protection Agency, which is an aggregation of four previously separate culture collections. The bacterial arm of it has around 5000 different bacterial cultures. I did do a quick check as to whether I could get a small sample of S. erythraea using my Debit Card, but you need to be officially registered before they start handing out the bacteria!
It's quite strange to think that these talks are actually taking place up in the north of the country while I'm writing this. Next year though, I'm aiming not just to turn up, but actually bring a poster with me, to show off some of my own work.
The Society for General Microbiology runs regular conferences that concentrate exclusively on the world of the very small. Although I am currently not a member :( I have been in the past, and plan to be again next year!
The conferences are always very good, and last august I bemoaned not being able to make one. This spring I am also not able to attend as I've only just come back from my honeymoon, and in the general scheme of work-life balance it would be a very sad and hardcore worker who would put an actual wedding second to marriage.
The last SGM conference that I missed, I decided to do a nerdy little one-women conference of my own, here at Lab Rat. And it worked so well that this time I'm going to try and do it again. One post every two days, covering the following topics in no particular order:
Seeing the cell through the “eyes” of the virus
Guarding microbial diversity
Life at Zero Growth Rate
Maths & microbes - heh that'll be fun!
Social evolution in micro-organisms
Seven topics, which should take me two weeks to get through. It'll be a good way to get my self back into blogging and back into the exciting world of bacteria. It should be an interesting fortnight!
Well, I know things have been a little silent around this blog, and there are a couple of reasons for this. One of them I can't say, and will be clear later, one of them is far too personal for a blog, and the other I feel I can share with any of my loyal readers who might have popped in to look at the cobwebs.
In less than a week, the Lab Rat is getting married:
Exciting though blogging is, wedding preparations have unfortunately had to take precedent, and seeing as I'm actually no longer working in a lab (and not regularly exposed to papers) it was quite hard to make time to find as much interested bacterial research as I would like.
I'll be back by the second weekend in April, and ready to start properly blogging again, probably twice weekly posts, and possibly some more exciting information...
And for those interested I'll be keeping the same name, I'll just be Mrs Lab Rat, rather than Miss Lab Rat. Hopefully some day Dr Lab Rat as well!
Neisseria meningitidis is a bacteria which lives in the throats of around 30% of the human population. In most cases it causes no problems at all and just exists as a normal part of the throat microbial flora. In some patients however it can start to colonise the bloodstream and brain, leading to cases of septicemia and meningitis which are highly dangerous and can be fatal.
The invasion starts with individual bacteria, which adhere to the epithelial cells that cover the inside of the throat. They then start to divide and proliferate to form large aggregated colonies. Within these colonies they are connected to each other, and to the epithelial cells, by protrusions from the bacterial cell surface called pili which are shown below for a wild-type (i.e un-genetically modified) Neisseria meningitidis:
Image taken from the reference below. The arrow points to one of the pili, and the insert shows a close-up of it.
These pili are often modified by the attachment of small molecules to the pili proteins, including the molecule phosphoglycerol (shown on the right for those interested in structure). To test the effects of the addition of phosphoglycerol, the researchers found which gene caused the addition of this molecule onto the pili (the pptB gene), and removed it from the cell. Without the pptB gene there was still the same number of pili around the cell, but they were not clumping together as much. Instead of the thick fibres seen in the wild type above (caused by large bundles of pili) only little stringy fibres were seen. These thin spindly fibres show that without the addition of phosphoglycerol, the pili cannot clump together.
This is important medically as Type IV pili bundle formation and N. meningitidis aggregation for infection are linked. Interestingly it was not the aggregation that was affected by removing the phosphoglyerol but the ability of individual bacteria to leave the aggregate to infect other parts of the body. In wild-type bacteria, the pptB gene is strongly activated only after several rounds of division within the aggregate, so it looks like the addition of phosphoglycerol acts as a switch, communicating to the bacteria that enough of them have aggregated and it is now time to leave. If the pptB is activated due to large numbers of bacteria it could act as a communication of the population density - signalling to the individual bacteria that the current location is far too crowded, and it has better chances of survival if it leaves.
--- Chamot-Rooke J, Mikaty G, Malosse C, Soyer M, Dumont A, Gault J, Imhaus AF, Martin P, Trellet M, Clary G, Chafey P, Camoin L, Nilges M, Nassif X, & Duménil G (2011). Posttranslational modification of pili upon cell contact triggers N. meningitidis dissemination. Science (New York, N.Y.), 331 (6018), 778-82 PMID: 21311024 --- Follow me on Twitter!