A bit of bat biology

Bats belong to the Chiroptera order of mammals, which literally translates from greek as 'hand wing'. This refers to the fact that they have the same bone structure in their wrists and hands as any normal mammal, however they are miniature in comparison, and have a thin membrane (also known as patagium) of skin that extends from their smallest finger, supported by other extended digits, which fuses to their abdomen to form wings. Fun fact: they are the only mammals capable of sustained flight. The more you know, right? Around 70% of bats are insectivores, and in many tropical regions they fulfil a vital role as pollinators, as they drink nectar and eat fruit from various plant species also. The 1,240 or so bat species that live on earth (we're not counting the bats that live on the moon here) are divided into 2 sub-orders: the less specialised frugivore megabats and the highly specialised echolocating microbats. The megabats, like the flying fox, are not nearly as elegant as the microbats. They're a bit like flying rodents in my opinion, in comparison to the feats of evolutionary engineering which can be seen in the microbat sub-order. By far the most impressive ability of the microbat is it's echolocation. The bats emit a cry, with frequencies ranging from as low as 11 kHz to as high as 212 kHz, which is reflected back at the animal from surrounding objects, allowing it to gauge size and distance. Bats use echolocation primarily for hunting, but again there are 2 different kinds; the frequency modulated (FM) sweep, which is a downward sweep through a range of frequencies, and constant frequency (CF) signal, which is a narrowband signal over one frequency. Both techniques have hunting applications, the FM signal is used for determining the distance between the bat and target prey for example, whereas the CF signal is used to calculate the velocity of prey. You can see why echolocation is so vital for insectivorous microbats (if you can't you have seriously missed my point here). Furthermore, there are specific situations in which bats must quickly adapt and change signal. An FM component in the cry is great when flying close to prey in an environment with many obstacles or for hunting individual moths in a swarm, but CF is used to scout out prey in an open environment, or by bats lying in wait to ambush prey. Bats have adapted their morphology to better suit echolocation, by having larger ears for example so more ultrasonic sound waves can be processed or by developing a basilar membrane within the cochlea of the ear, so the bat can tune their ears for narrow frequencies reflected from flying insect prey.

Anyway, that was my attempt at doing a halloween related post... with a biological twist.

EPIc GENETICS

Epigenetics is basically the study of chemical modifications to DNA, which do not alter the genetic code itself, but the molecules involved do act to silence or promote gene expression. There are many different mechanisms involved in this process, but today I'm going to take you through my top 2. The first is known as DNA methylation. This is simply the addition of a methyl group to a base of the DNA (cytosine is converted to 5-methylcytosine for example), and it is controlled by 3 different enzymes: DNA methyltransferase (DNMT) 1, DNMT 3A and DNMT3B. These enzymes are examples of epigenetic "writers" (thank you Nessa Carey for the great analogy), as they actually create the epigenetic code, by adding methyl groups to CpG motifs of genes, creating an epigenetic mark. Highly methylated areas of the genome are less transcribed than those areas with fewer methyl groups added. But DNA methylation does not occur randomly, because most CpG motifs are concentrated just 'upstream' from specific genes, in their promoter regions where transcription factors usually bind. These are called CpG islands, and in around 60% of protein coding genes the promoters lie within these islands. Methyl groups binding in the CpG islands inhibit transcription factors from binding in the gene promoter region, and therefore more methyl groups = less transcription.

The other epigenetic mechanism that I particularly like is the histone modification; acetylation. Histones are proteins which chromosomes are bound to, in order to package DNA into nucleosomes, and acetylation involves adding an acetyl group to a specific lysine amino acid on the N-terminal tail of a histone (lysine converted to acetyl-lysine). Again, the acetylation does not alter the underlying genetic sequence, however it does promote gene transcription. Usually the reaction is catalysed by histone acetyltransferase, and is important in regulating transcription factors and effector proteins in our genome. The problem with histone modifications is that there are so many different processes, with different effects on gene expression, that a complex histone code is created. Even geneticists find it difficult to get to grips with, so let's not go into that...

The fastest protein, based on a fictional blue hedgehog...

What is it with geneticists and video games? In his book 'Your Inner Fish', Shubin describes the Zone of Polarising Activity, which is a tissue present in early embryos. It contains signals which instruct developing limb buds to form along an anterior (nearer the front)/posterior (nearer the back) axis, so the thumb and smallest finger are correctly differentiated. An essential gene that must be activated within the ZPA during the 8th week of embryonic development is known as the Sonic Hedgehog gene (insert Pewdiepie Sanic reference). It codes for a protein called, once again, Sonic Hedgehog, which is an essential ligand on the hedgehog signalling pathway. This pathway is vitally important for organogenesis in us vertebrates, the process by which the ectoderm, endoderm and mesoderm primary germ layers on an early embryo develop into working organs, and obviously digit formation, which is why the Sonic Hedgehog gene is needed in the ZPA. The SH protein is also required to organise the brain into its different zones, cortexes and bulbs, and is one the best known examples of a morphogen. Apart from sounding a bit like an evil gelatinous mass bend on destruction, a morphogen is a chemical that causes an organism to develop its shape. The SH protein molecules can diffuse, to create concentration gradients in different tissues of the embryo, and the concentration in the cells of these tissues has a profound effect of what SH's function is. That is why it is able to cause differentiation of the digits when active in the ZPA! And so we have come full circle, and we now know that there is yet another essential protein in our bodies, with nomenclature based on a video game character, who is in Super Smash Bros... So where's the Shulk gene then? *laughs awkwardly*

My favourite protein

Pokemon has always been an inspiration for me. It's what kindled my love of the natural world, despite my urban upbringing. So when I discovered that a protein was named after the beloved mascot of the franchise, Pikachu, I just had to check it out. The protein, named Pikachurin, is essential for our vision, as it it plays a role in the delicate and precise interactions between the photoreceptor ribbon synapse, which is essentially a neuronal synapse connected to photoreceptor cells in the retina where the phototransduction of light into electrical impulses which travel to the CNS occurs, and dendrites. These dendrites act to increase the conduction of electrochemical stimulation received from the light receptive rod and cone cells in the eye, and pass it on to the main cell body of the sensory neurone, so it can travel to the brain. To do this Pikachurin must bind to the less interestingly named Dystroglycan protein. However, incorrect binding of the 2 proteins can result in ocular dystrophies, in which the tissue cells in the eye die prematurely and vision is lost. But why was it named Pikachurin I hear you cry? Well, because the protein in nimble, and pikachu is well known for its speed, and electric attacks (get it? like the electrical impulses that cross the photoreceptor ribbon synapse... SCIENCE BANTER!) Pikachurin may even have therapeutic applications, as the Osaka Science Institute, aptly located in Japan-the birthplace of pokemon, is researching how the protein could be used to treat retinitis pigmentosa, and restore sight to those suffering from the retinal dystrophy. I never could have guessed that such a relatively frail, electric mouse pokemon, that needs a light ball to have any competitive application in the metagame, could inspire the nomenclature for such an essential protein. 

Bovine Tuberculosis: should we be worried?

Continuing on the with the theme of deadly microbiology, let's take a look at Myobacterium bovis, or Bovine Tuberculosis. The bacterium has received A LOT of press coverage here in the UK, and for good reason. In 2012, 38,000 British cattle were slaughtered because they tested positive for the disease. This is because bTB is extremely efficient at spreading through an organism. It is transmitted in the air via droplet infection (just a few bacilli in a tiny fluid droplet), and when it reaches the bronchi, phagocytes move to intercept and digest the microbes. However this plays to the bacterium's advantage, as it can move into and replicate within the white blood cell. The phagocytes continue to pour into the lungs, in a largely unsuccessful attempt to destroy the invading pathogen, and the bacilli continue to replicate inside them, and eventually a tubercle is formed. The tubercle is like an undetonated warhead, and as soon as it bursts M. bovis pours out onto the lungs, causing a potentially deadly infection. The test for it involves injecting a small amount of both avian and bovine tuberculin into the skin of an animal. If an animal is infected, it will display a localised allergic reaction (in the form of swelling) a few days after the injection. But how does the bacterium spread from herd to herd? Well, 30 years ago DEFRA discovered that badgers are carriers of bTB. The RSPCA estimates that 4-6% of UK badgers are infected, and around 2,000 die every year from the fluid filled lungs which result from a bTB infection. Badgers are being culled in the UK by trained marksmen, however there have been reports of unethical set gassings and poisonings. The only vaccination currently available for cattle; the Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine, is illegal under EU law, as an animal injected with it is indistinguishable from an animal with bTB (obviously, the vaccination is just an inactive form of the pathogen). However the vaccination is being used to treat badgers, so there is a glimmer of hope here. Furthermore, the Environment secretary Elizabeth Truss recently launched her Badger Edge Vaccination Scheme, which supports the vaccination of badgers using  BCG, in areas around the current cull zone in Gloucestershire primarily. This creates a 'buffer zone' of healthy badgers, to stop perturbation, the movement of badgers outwards from their area of origin due to ineffective culling methods,  from spreading bTB into previously unaffected areas. There have even been cases of bTB being carried by domestic cats, which pass it to their owners!  So should we be worried? If bTB continues in this way, a whole industry will go into a spiral of decline, and Britain will lose a valuable export. However there is minimal threat to human health from the pathogen. That's good...right?

10th post special: How to weaponise a pathogen

The outbreak of Ebola in West Africa has been a huge news story over the past few weeks. 4,000 people have died from the virus, which currently has a 70% case mortality rate. Maybe it's because I'm a little crazy, but whilst reading about ebola I thought: why has no-one attempted to weaponise ebola yet? I mean, ISIS, or whatever they're called this week, wouldn't have to worry about guns and bombs, if they could wipe out western civilisation with a microbe! But actually, attempts have been made to weaponise ebola, although not entirely successfully... The Japanese terrorist/general crackpot cult Aum Shinrikyo, responsible for the gassing of the Tokyo subways in 1995 by producing sarin gas (the solid and liquid reagents in plastic bags were wrapped in newspaper, and punctured with umbrellas as cult members got off the train, allowing the deadly reaction to occur), made an attempt to obtain ebola cultures for weaponisation in 1992, under the guise of providing aid during an outbreak in the DRC. However they failed spectacularly, and returned to Japan without a single culture. That's all well and good, but how would you go about creating a strain of ebola that develops resistance to vaccines and antibiotics faster, transfers the resistances to other individuals, with increased virulence, a greater range of potential hosts and that would evade detection? I struggled to find any information on precisely what part of the viral genome you'd have to modify to make ebola even more infectious, although ebola's genome is composed of only one strand of RNA 19,000 nucleotides long. It only encodes seven structural proteins: nucleoprotein (produces more nucleic acids), polymerase cofactor (chemical compound required for polymerase enzyme to copy RNA), GP, transcription activator (promotes transcription of genes) , VP24, and RNA polymerase (copies RNA). All of these structural proteins are vital for viral survival, but the transcription activator protein is what we're looking for here. In ebola the transcription activator would bind near the promoter region on a gene, and forge protein-protein interactions with the transcription machinery, like the RNA polymerase, promoting gene transcription into mRNA, which can then be translated into protein. If you could artificially modify genes coding for the transcription activator, by say histone modifications (can you even do that in viruses?), to produce more of the protein, it could have the potential to supercharge viral replication inside host cells, so they could lyse more host cells at a faster rate, thus killing the organism faster. But that's only skimming the surface of what's probably possible with the right technology and knowledge. Conspiracy theorists take note, we may have a future government experiment on our hands...

Revealed: the chameleon's disguise

Who hasn't dreamed of having a chameleon as a pet? Just me? Oh, ok then. Anyway, I've never understood the the biology that allows them to change colour dependant on mood or surroundings, so I thought I'd do a little research... I discovered that chameleons have a transparent outer skin, below which there are 3 layers of specialised chromatophore cells with chemical pigments in their cytoplasm. In the top layer, the chromatophores used are known as xanthophores and erythrophores, which contain yellow and red pigments. The second layer contains iridophores and guanophores, which contain guanine and contain the blue/white pigments. The 3rd and deepest layer of chromatophores, known as melanophores, have a slightly different and all together more interesting function. They are the cells which control how much light is reflected back from these 3 layers, to adjust for light intensity. The intensity of the colours given off is determined by the distribution of pigment molecules within the cells- if these molecules are spread all over the cytoplasm, the colour given off is more vibrant. But the chameleon can also make these cells transparent by concentrating the pigment in the centre of the cell. The reptile is able to rapidly reallocate the pigment molecules, allowing the colours to shift wildly like a bad LSD trip. But why go to all this trouble to develop such a mechanism? Many believe that it is so chameleons can blend in with their environment, however for the majority of chameleons this is not the case. Most species use their colour change ability to signal to other chameleons their physiological condition and their emotions; for example they show darker colours when angry, to intimidate foes. The Namaqua chameleon species even uses the ability to help regulate its body temperature (homeostasis yo!), turing a light grey colour during the heat of the day to reflect infra red radiation from the scorching desert sun. As Adam Savage might say: MYTH BUSTED! Woa Woa Woa, hold your horses there! Why do chameleons bother with such a complicated mechanism, which could be almost entirely replaced by simple body language to portray emotions? Most of the animal kingdom uses body language for intraspecies communication. However I have a theory: because chameleons rely on an element of stealth and patience to catch prey and evade predation, they cannot afford superfluous motion which may give them away to other species. Therefore they use colour changes which not all predators/prey have the optic capability to see, in order to communicate. That is their ecological niche. It all fits rather well doesn't it? Although I can't prove this hypothesis without data...this isn't Philosophy! (joking).

Is evolution lazy?

I've always thought the motto of evolution and natural selection to be: 'If it ain't broke, don't fix it'. Take plants for example, their chlorophyll has a green pigment meaning it reflects all green light, and it can't be used in photosynthesis (plants only absorb 3% of light that hits their leaves). Why isn't the chlorophyll red, or yellow, or colour that excludes less light though? Well the explanation for that is simpler than you might expect; because during the trial and error phase of the chlorophyll development in evolution, green was probably tested, it worked well enough for plants up to a certain size to meet their sunlight absorption needs, so it was kept. The plants weren't exactly capable of testing the best pigment colours in a longitudinal study; once they found one that worked, they kept it, and 'if it ain't broke, don't fix it'. This may be the reason that plants don't have a central nervous system like animals do. For animals the CNS is vital, as we need brains capable of problem solving, fast impulse conduction from sensory organs via neurones, co-ordinated movements, and the ability to feel pain, in order to survive as omnivores, in finding food, remembering the best places to find said food, evading predation, reproducing and to find suitable habitats. Whereas plants can survive perfectly well using photosynthesis to produce sugars, relying on insects and the wind for pollination, and using plant growth chemicals like auxins to respond to environmental stimuli in like sunlight (phototropism) by promoting cell division or elongation, because plants don't have an endocrine system like animals do. But it's because they don't need one to survive, that they don't have one. Plants have never needed to evolve a CNS by natural selection to survive, as they can produce all they need as stationary entities, without the need for complex thought or electrical impulses, ergo they don't have a spinal cord or brain. Because 'if it ain't broke, don't fix it'...

I am Groot?

We've all seen the wonder of science fiction that is, Guardians of the Galaxy, right? Well it contains some outstanding scientific achievements, like a cybernetic and overly narcissistic racoon, a vacuum repelling face mask, a black hole grenade, space shuttles capable of time dilation and, what I found most fascinating, a sentient, mobile tree-like organism. That got me thinking, why are there no such life forms on this planet? What stopped plants from developing a CNS + receptors, and becoming as developed as we are? It may be an ambitious aim, but I'm going to try an find out why we are not Groot... so to speak.

Lets start at the beginning, with LUCA (Last Universal Common Ancestor), a bacteria-like organism that lived deep below the earths surface around geothermal hotspots. So it obviously didn't contain chloroplasts for photosynthesis, it in fact used chemiosis, the generation of ATP by the movement of hydrogen ions across a membrane, for its energy. It contained DNA and RNA, with a genetic code composed of 3 base codons, and 80s ribosomes like all eukaryotic life on earth today. Just by looking at the phylogenic tree of life, derived from ribosomal RNA sequence data, you can see that animals and plants only branched from each other relatively recently on the eukaryota arm of the tree. What caused this divide between plant cells and animal cells you may be asking? Well, what could have happened was that during the eukaryotic cell's evolution, it ingested a smaller prokaryotic cell via endocytosis, and the prokaryote just happened to contain the organelles required for photosynthesis. This new combination thrived and became an entirely new brach of our phylogenic history, the plants. They use a complex electron transport chain between 2 photosystems and photolysis to generate NADPH and ATP, which then goes on to produce glucose in a light independent reaction. Whereas animals get their glucose from what they consume, and their ATP is produced via the Krebs cycle and another electron transfer system.

There are definitely other factors that led to this separation, however the key principle to understand here is that plants and animals are fundamentally different organisms, with little overlap in their phenotypes at least. The mechanisms they use to produce ATP , are different enough to warrant such different forms for these organisms, developed through evolution, a topic I will discuss further in my next post...

The mechanism of bruising

Over the weekend, whilst I was being pelted by a firing squad of my friends with the dangerous, high velocity weapon that is a football, I asked myself 2 things. One, why do I play as a goalkeeper? Two, what causes the myriad bruises that bloom across my arms and legs in the aftermath of my exploits defending a string netting and metal frame from a rubber ball? Well, I discovered that the discolouration under the skin is caused by cells bursting open and spilling their contents; the organelles and everything else in the cytoplasm. This happens due to trauma induced premature autolysis- basically the force of the ball hitting my limbs, causes cells to digest their membranes with their own hydrolytic enzymes, in a process known as necrosis. Who knew such an everyday thing like bruising could be so interesting? However, I also discovered a second type of cell death, known as apoptosis. Apoptosis is altogether more natural and controlled carefully by the body, also known as programmed cell death (PCD). Apoptitic proteins target the mitochondria of cells, and can effect them in different ways, for example by the formation of membrane pores, or an increase in the permeability of the mitochondrial membrane, which in turn causes apoptotic effectors to leak out. Either way the mitochondria is destroyed, and the cell cannot respire aerobically, so it dies. There is also a pretty complicated process involving direct initiation of apoptotic mechanisms, and there are seemingly 2 rival theories: the Tumour Necrosis Factor model, and the First Apoptosis Signal model. Anyway, unlike necrosis, apoptosis produces cell fragments called apoptotic bodies that phagocytic white blood cells are able to engulf and quickly remove before the contents of the cell can spill out onto surrounding cells and cause damage. Pretty neat huh?  And in an average human adult, around 60 billion cells die each day due to PCD, which seems like a lot until you consider there are around 37 trillion cells in our body. How all these cells organise themselves into complex structures, and work together in near perfect unity, is part of the reason I never ceased to be amazed by the field of Biology.

The fantastic four

Before I launch lead long into the field of epigenetics, I would just like to explain what a stem cell is. The pluripotent stem cells, generally thought of as the gold standard of stem cells as they can become any cell type other than placental tissue, we can harvest from a blastocyst early in development. The inner cell mass, that would become the embryo later on, is removed from the trophoblast (the developing placenta) and specially cultured to form pluripotent Embryonic stem cells (ES cells). They may be difficult to produce, but these ES cells can divide an infinite number of times, and if you have the right culture conditions, you can make almost any cell type. For example ES cells can differentiate into autorhythmic cardiomyocytes that beat, if you can imitate the conditions of the heart in a culture.

Now onto the main course, the Japanese doctor-turned-geneticist Shinya Yamanaka. Yamanaka spent a huge amount of time and resources trying to identify the genes expressed in ES cells, which allow them divide infinitely and differentiate into almost any other cell, but which are silenced after the cell has differentiated. He started his investigation with a list of 24 genes, knowns as 'pluripotency genes', which were thought to be vital in ES cells.  Yamanaka tested combinations of these genes, to see if they would cause a differentiated cell to move back up Waddington's epigenetic landscape(picture on right) and become pluripotent again, a huge risk to take - putting his career on the line for scientific progress; that's what I call dedication. He tested the combinations of his 24 genes in mouse embryonic fibroblasts (connective tissue cells) (MEFs). These cells were taken from embryos, as the name implies, and Yamanaka was hopeful that they would retain some of their capacity to convert into early cell types in the right culture. However, the mice cells used were special, they contained an extra gene known as the neomycin resistance gene, giving the cells resistance to the normally deadly compound neomycin. The gene was inserted into the genome in a way that meant cells would only express it, and survive neomycin if they became pluripotent. When all 24 genes were inserted in vectors simultaneously, only a tiny fraction of cells became pluripotent and survived the neomycin. However, the winning combination, of only 4 genes in fact, was;Oct4, Sox2, Klf4 and c-Myc. These 4 genes allowed cells to survive neomycin poisoning, and even change their appearance to look like ES cells. Yamanaka christened his discovery 'induced pluripotent stem cells', and the 4 genes are forever known as the 'Yamanaka factors'. What I find most incredible about this breakthrough is, that despite the fact our cells contain around 20,000 genes, only 4 are required to produce a pluripotent cell. It just goes to show the immense power even individual genes wield within the human body...

Toadspawn: the making of a Biology legend

John Gurdon. Does that name mean anything to you? If it doesn't, and you call yourself a biologist, stop now. I saw a job vacancy at the local Tesco Metro. Anyway, John Gurdon is a legend in the world of biology. He started his research on the African clawed toad, Xenopus laevis, to determine whether tissue cells from an adult toad still contained all the genetic material they started with as a blastocyst, or whether they had 'lost' some of this DNA as the cells became more specialised. He did this using the SCNT process (Somatic Cell Nuclear Transfer for the uninitiated), where he transplanted a nucleus from a somatic cell of an adult toad into an enucleated egg cell, which is then given an electric shock, to stimulate mitosis, and the cells are transplanted into a surrogate mother. Gurdon then kept the resulting eggs in a suitably controlled environment. The nucleus from the adult toad somatic cell was relatively unsuccessful at producing tadpoles, however this was irrelevant. He had proved that, genes are not permanently lost during cell differentiation, they were just deactivated. Putting the nucleus in the right environment, like an egg cell, allowed the cell to move back up Waddington's landscape of differentiation and, if not entirely successfully, reactivate the genes required for blastocyst development. This means the cell was essentially made pluripotent, and whatever was 'silencing' the genes in a differentiated cell, was 'wiped off' in the enucleated egg's cytoplasm. Although he was oblivious to it at the time, Gurdon's work was the dawn of a new age for genetics. The age of Epigenetics.

To be continued... (the suspense though!)

Entropy: the chemistry of chaos

Entropy was an idea first conceived by Ludwig Boltzmann, an Austrian physicist credited as the father of statistical mathematics: which explains and predicts how the properties of atoms, like mass or charge, determine the physical properties of matter, like viscosity or diffusion rate. He called it the H-theorem (S=K logW - the inscription on his gravestone too interestingly), which basically boils down to the 2nd law of thermodynamics; the entropy of a closed system always tends towards a maximum. So the universe essentially wants to be as chaotic and disordered as possible, at least, that's how I understand it. That's why a dissolved substance remains in suspension I guess, because a liquid has more entropy than a solid, as it's particles are sort of random and can flow-they don't just vibrate around fixed points like in a solid, and the closest the dissolved solid can come to maximum entropy is being in an aqueous solution. That's all well and good, but how does that link to biology?, I don't hear anyone scream. Good question, and here's where entropy gets interesting (for me at least). 


As Erwin Schrödinger so eloquently put it, living creatures 'drink orderliness' from their environment. Take any tree-dwelling Arboreal Gecko for example, they eat insects, and those insects are broken down into their constituent elements by enzymes and acids etc in digestion, and mostly assimilated into the Gecko's flesh. In a world that tends toward disorder, these Gecko's are performing an amazing feat. A gecko may be an open system, with inputs and outputs, which means it does not violate the 2nd law of thermodynamics, which assumes a closed system, but what they actual do seems so obvious on the surface, but is still truly incredible if you open your eyes. They have bodies. These bodies are vessels for order, allowing the Geckos, or any other organism for that matter, to become more complex, without the disorder of the universe driving them backwards, and they expend a lot of energy doing so. So there you have it; never take your body for granted, as not only is it a biological wonder the like of which earth has never seen before, it is a rare piece of tranquility in the calamity that is the universe.