Dear Chelsea

 I’m sure nobody can even view this blog anymore, but maybe like a message in a bottle it’ll find its way to you. I wish I’d been brave enough to say hi when we passed in the hall at RVC a few years ago. I tried to finish my BSc but despite the support of a wonderful friend group I didn’t have it in me after year 2. I dropped out and drifted aimlessly for a while until I got a job caring for dogs. It’s not exactly a STEM field but it’s fulfilling. I really hope you found a career you enjoy doing. 

I’m so grateful you got me into Magic! I still play Commander every week at Dark Sphere in Shepherd’s Bush, and I’ve met so many wonderful people through it. I also still play Guild Wars quite a lot, and got really into raiding last year. Do you still play? 

It’s been so long since we last spoke, maybe the version of you I knew doesn’t exist anymore. Maybe the version of me you knew doesn’t exist anymore? Regardless, I miss you and would love to catch up.

Love, 

Niamh 

Our 'La La Land'

Musicals aren't usually a genre of film that capture my attention, or hold it for that matter. However, I somehow ended up seeing 'La La Land', and it struck such a chord with me that I am writing this as I leave the theatre. In some weird twist of what some may call fate, life threw at me a movie I needed to see, and a perspective that I had never considered. Perhaps one day, five years from now, we'll catch each-other's gaze across a crowded room, and think of what could have been. Everything else will fade away as I stare into your eyes, and see us navigating the treacherous ocean of life together, as though we were never apart. Maybe then I'll be able to smile at you, and think to myself that it was all worth it. "I always loved you".

'Junk' DNA vs The World 2

Looking over the skyline of Camden as the sun sets on my first day of university life, I begin to to contemplate my place in our world. How much impact could I ever make? I am one average person in virtual sea of more prolific people, all trying to find meaning in an existence that intrinsically has none (I blame the Satorl Marsh night theme I'm listening to for that last bit). But my existential crisis aside, I did begin to think about the human genome, and how the neglected 'junk' elements of it must feel, always being in the shadow of the protein coding genes, which have a reputation as the be all and end all of molecular biology. Although personifying genetic material is not really a valid way to think about the issue... Therefore I will once again champion the Junk DNA in its quest for genomic appreciation. As I stated last time, human proteins are often the same size as equivalent proteins in simpler organisms; it is the sections of intervening junk that increase in size as the complexity of an organism increases. This creates what Nessa Carey describes as a large 'signal-to-noise ratio' during analysis of genes within our genome, as there's only a relatively small region that codes for protein, embedded in a large section of junk. But this DNA must have a role to play, otherwise we would be no more complex than a fly or a worm... (only a slight exaggeration...) Some complexity is added by post transcriptional modification of mRNA, in a process known as splicing. In splicing the exons, sections of DNA which code for proteins, are cut away from the intron sequences (the junk), and can be arranged in various fashions to generate different mRNA molecules from the same gene. Over 60% of human genes produce multiple splicing variants, however this only goes so far in explaining our relative complexity. Back in 2001, in the wake of the Human Genome Project, researchers thought the junk may not even have a functional role, as the pufferfish Fugu rubripes has a genome 13% the length of our own (devoid of much of the junk we see in our genomes), and is still a successful organism. It was hypothesised that the junk was parasitic, selfish DNA using our DNA as host for future proliferation (I just can't escape you Richard...). Although based on what we know about evolution, it is irrational to assume that just because the DNA has no obvious function in one organism, it does not mean it is useless in all organisms (especially in more complex species). One theory supporting the importance of junk DNA states that it could act as mutation insulation for the protein coding genes, as it makes it decreases the likelihood that a point mutation will affect a protein coding sequence, a benefit of the large 'signal-to-noise ratio'. The reason humans would need more mutation insulation than simpler organisms is because we have longer life spans, and therefore we accumulate more mutations, and we also produce fewer offspring, so it is beneficial that they are better protected from mutations in order to ensure species survival. In terms of cost-benefit, it isn't worth expending resources in simpler organisms to protect protein coding genes, as even if they accumulate a mutation they are still viable (fewer systems can be affected by the lack of protein production), and the offspring will likely still survive and breed (ah the virtues of simplicity). So who's irrelevant now 2001 geneticists? But seriously, if the junk DNA is used as a buffer for mutations, which have the potential to disrupt vital metabolic processes for example, is the nomenclature 'junk' still applicable? Not in my book, and this is my blog. Deal with it. How empirical of me.

'Junk' DNA vs The World

Proteins, proteins, proteins; Biologists are obsessed with them. Sure they are the reason us complex organisms can exist, but as a result of this infatuation with our polypeptide friends, we often overlook a rather important aspect of the human genome. Only 2% of our genome codes for proteins, and so until recently a large proportion of the other 98% was dismissed as 'junk' DNA. However, we are now realising that proteins may be the final end points required for life, but they could never be properly synthesised and organised without the junk genetic material. In fact, research into the genomic differences between more complex and simple organisms has concluded that the only genetic change that occurs as biological complexity increases is a greater percentage of DNA that does not code for proteins. Junk DNA can code for RNA, not the mRNA that is used for translation of proteins, but RNA that is functional in its own right! (more on this later) I personally feel betrayed by the A-Level Biology syllabus at this point... Anyway, the fact that Biologists were so focussed on the effect mutations had on protein coding DNA, meant that they were looking in the wrong neighbourhood of the human genome for the cause of inherited disorders like myotonic dystrophy. Within the myotonic dystrophy gene, a small base sequence (CTG) is repeated multiple times; 5-30 repeats in a healthy person. If the number of repeats exceeds 35, the sequence becomes unstable and can change in number erratically from one generation to the next, and as the the length increases generationally, the symptoms of the condition worsen, and develop earlier. At this point you're probably thinking; this is just a standard change in the base sequence of the gene, inhibiting the production of the correct protein. However, you would be wrong, as the amino acid sequence produced by this mutated myotonic dystrophy gene is unchanged, and the protein is still synthesised (did I just hear the jaws of the uninitiated drop?). Is this just an anomaly perhaps? Certainly not. Fragile X syndrome, the most common inherited learning disability, and Friedrich's ataxia, a muscle wasting disease, follow a similar mechanism. This was an unnerving revelation for researchers; there are mutations that can cause disease without changing the amino acid sequence of proteins. But in that case how do sufferers develop such debilitating symptoms? In Friedrich's ataxia, much like in myotonic dystrophy, the abnormally large section of repeats (GAA in the case of FA) is found between 2 sections of the protein coding genetic material(so in the junk DNA). Research has shown that when cells contained the expanded repeat, the production of mRNA encoded for by the gene was inhibited. The enlarged section of GAA repeats prevents accurate copying of the DNA, and thus there is no translation. In the case of Fragile X syndrome this means RNA around the cell is not properly regulated by Fragile X protein, causing cellular chaos and a life of disability for the sufferer. But that begs the question; why have the repeat sequences within the genes for myotonic dystrophy for example, been conserved over our genomic evolution? I mean, the repeats are located at the very end of the gene, so could easily be left out of any RNA produced. This means they must have a purpose in a healthy cell, within the mRNA of the gene. This is in fact the case, as the myotonic dystrophy mRNA is used to bind proteins in the cell (a weird role for mRNA), and the larger the repeat expansion, the more molecules are bound. The proteins are normally involved in the regulation of other mRNAs; controlling their lifespan and translation efficiency, and so without these regulatory polypeptides, the cell cannot function correctly. This discovery made sense to clinicians, as diseases in which a small change in gene expression creates such a huge impact on a patient, with fine tuning of severity between patients (based on length of repeats), are simply not observed. Therefore the role of this mutated junk DNA is more complex than we first thought, as it is not simply the number of abnormal repeats within the DNA that affects symptoms, but also the role of the expanded section of repeats on the mRNA synthesised from the mutated section of DNA in gene expression. From this paradigm it is clear that the fact that we have sequenced the human genome does not mean we understand all of its intricacies. Junk DNA has a powerful role, not just in inherited diseases, but in almost every aspect of our genome, and even our epigenome. That is why I'm so excited to continue this series, shedding light on the enigmatic sections of the genome previously condemned as insignificant junk.

The rise of the 'Dino-Chickens'

The first Archaeopteryx fossil was unearthed from a limestone quarry in Bavaria, in the early 1860s. This relatively small (Raven size as an adult), feathered, broad winged dinosaur is believed to have glided like a bird through the forests of the Jurassic period 145 million years ago, leading many palaeontologists name it the ancestor of modern birds. Phylogenetic study is never so clean-cut however. Therefore it is unsurprising that other species similar to archaeopteryx; Aurornis xui, and the four winged Anchiornis huxleyi for example, are also contenders for the title of the first bird. But why are our winged dinosaur friends relevant? Well in May 2015 scientists were able to 'alter' chicken embryos to produce a dinosaur-like snout, which was an amazing breakthrough given the lack of clarity in the evolution of dinosaurs into birds; there is no single physical feature that defines this phylogenetic change. One important phenotypical transition evidenced by fossils was the alteration of the premaxilliae in the reptilian snout, growing longer and fusing together to form the beak structure present in birds today. The research team from Harvard then looked at gene expression domains in the face of multiple bird and reptile species; the earlier frontonasal ectodermal zone (FEZ) and the later midfacial WNT-responsive region (they sound incredibly intellectual but rather arbitrary at the same time). From this the researchers reasoned that reptile and dinosaur snouts develop from premaxillae in a similar way, and that the developmental pathways that form the snout were altered in the course of the evolution of Aves. 2 proteins; FGF and Wnt, were found to be essential in the differing developmental process of reptile and bird faces, due to differential gene expression and therefore differential translation of these proteins. The proteins worked differently also, as in reptiles they were active across 2 small regions of the embryo's 'face', whereas in birds they were expressed across a larger band, but in the same region as in reptiles. This may be evidence that evolutionary alteration of expression of these proteins contributed to beak formation. To test this theory and the mechanism of the snout to beak transformation, the autapomorphic median gene expression region found in birds (the area of the genome coding for the beak) was altered in developing chicken embryos. Biochemical inhibitors were added to the chicken eggs to block the 2 vital proteins, thus reverting the chicken's beak to its ancestral reptilian snout, with the premaxillae formed showing a resemblance to fossil specimens, rather than beaked birds. If you're like me though, the term 'biochemical inhibitors' is far too vague. So what do they do exactly? I believe they alter the epigenome of the chicken embryo, perhaps removing methyl groups from CpG regions of long silenced genes, or they may involve acylation of the tails of histones (perhaps using histone acetyltransferase enzymes) to alter transcription rates of genes (See my previous posts for more on epigenetics, it's my favourite thing ever). Back on the Dino-Chickens; let's not get overexcited about a potential Jurassic World situation happening where we reverse engineer dinosaurs and splice them all together into ridiculously improbable 'combosaurs'. The team from Harvard was only seeking the mechanism behind ancestral amniote snout transformation. But perhaps in the future... My army of squid, poison dart frog, chameleon ankylosaurs will become a reality!

Zombie Apocalypse anyone?

"Brains..." That is what most of us Western World dwellers think of when the topic of the undead is broached, however most of us are clueless as to the origin story of our beloved halloween staple; the Zombie. I would like to dispel this ignorance, but at the same time give a real world example of where zombification (It's a word now, deal with it) is an all too real occurrence, but also how it can even happen. Our story begins in Haiti, where rural folklore describes necromancers, who supposedly used magic to commune with or summon the dead, and had possibly the most epic job title ever. These Zombies would become mind-slaves of the necromancers (but they were not called Steve weirdly), and had no will of their own. The root of such folklore lies in Africa, and was likely exported to Haiti via slavery. The African slaves believed that Vodou deities would resurrect them and take them to the heavenly afterlife in their home continent. Western Zombies just seem uncultured and dull compared to the Haitian legends, you might say they pale in comparison... (I'm not entirely sure that made sense). That's enough history for today, let's get our biology on! The real world Zombie-esque paradigm we shall confront involves the sophisticated predator that is the Ladybird, and a wasp of a parasitic persuasion. Did you know Ladybirds use their antennae to detect chemicals that plants release when under attack by herbivorous insects like aphids (the Ladybird's main prey), and they can bleed poison from their legs to dissuade predators? The fact that they are so effective within their niche was why it came as a shock to me that they are vulnerable to zombification. The parasitic wasp in question, Dinocampus coccinellae, uses its stinger to inject an egg into the Ladybird's underside, along with a venom. Once the larva emerges, it feeds on the fluids that fill the Ladybug's thorax cavity. Externally, the insect is still behaving normally, eating aphids with its usual fervour, which in turn feeds the parasite growing within it. This is where it starts to get upsetting, so please if you have a weak heart or a particularly irrational attachment to the Ladybird, stop reading now. After 3 weeks of 'gestation', the larva squirms out through a weakness in the Ladybird's exoskeleton, and creates a silk cocoon for itself below its host. The Ladybird remains under the control of the parasite though, and so stays perfectly still during this process, apart from when the wasp larva's predators approach. The Ladybird acts as an insect shield for the D. Coccinellae by spasming its limbs to scare off Lacewing larvae for example. This continues for a week, until the adult wasp cuts itself free of the cocoon with newly formed mandibles and flies away, finally deigning its enslaved protector to die... But why did such mind controlling, zombie-making parasites even come to evolve? The answer, like just about everything on this blog, lies within the genome of the organisms. Genes use organisms as vehicles to increase their own replication success, and the phenotype created by the genes is vital in this process. The phenotype is not just limited to dictating the appearance of an organism. It can profoundly alter the organism's environment, as the phenotype extends to structures in the brain which produce specific behaviours. So if a gene is powerful enough to alter a physical environment, then could it manipulate another living creature? The fact that parasites can manipulate their hosts is because of transcription of genes and resultant translation into necessary proteins, and if a mutation changes the base structure of the genome, the way in which the parasite influences its host's behaviour will change, and those parasites that produce the most offspring have developed a mutation that changes the host's behaviour in a favourable way. For example the parasitic wasp genome that codes for venom molecules that cause the Ladybird to act as a bodyguard for the growing larva will be more successful, and so the genes which dictate this will be found in higher frequencies in offspring and therefore in the gene pool of the species as a whole. In this way the need for genes to preserve themselves and increase their chances of wider replication affects the behaviour of another organism... So there you have it; the genetics behind the development of such extra-ordinary mind controlling (zombifying) powers. It was never necromancy, just egomaniacal genes. Biology wins over popular culture and mythology once again! (In my head at least)

The hardiest bear that never was

Just over a month ago I visited the American Museum of Natural History in New York City. There I was fascinated with the phylogenetically accurate layout of fossils over the museum floorspace, showing the evolution of fish to amphibians, and then to reptiles (no Tiktaalik unfortunately) for example. During my visit I was also enraptured by an exhibition entitled; Life at the limits: Stories of Amazing Species, as one particular species stood out to me as the star of the survival show.
What if I told you there is a species of 'bear' that has existed on earth since the Cambrian period, around 500 million years ago? The word delusional would most probably spring to your mind, however I have evidence from the fossil record. Perhaps the word 'bear' was disconcerting, as I did not mean a member of the Ursidae family, but in fact a species known as the Tardigrade (me and my science word plays...). The Tardigrades have nicknames such as Water Bears or Moss Piglets, perhaps due to physical appearance (I don't see it personally, but they are kinda pudgy) and their favoured habitats; films of water that cling to mosses. Tardigrades are a large group of animals, consisting of 1,150 species, that includes some of the toughest creatures in the world. They can be found the world over; from the Himalayas 20,000 ft above sea level, to the deep sea 13,000 ft below sea level, even in the polar regions and on the equator, where the environment is hardly accommodating. Although I wouldn't hold out any hope of seeing one with the naked eye, as most individuals range from 0.3 to 0.5mm long. The Natural History Museum exhibit depicted the survival abilities of these organisms as a cycle, which I thought worked rater effectively. First, when their surroundings become intolerable, certain species of Tardigrade are able to deflate, draw in their legs and coat themselves in a waxy substance. The resulting structure is called a tun, and is barrel-like in shape with the creature's claws protruding from it. In this state tardigrades are capable of reversibly suspending their metabolism in cryptobiosis, and many members of the species can regularly survive in this state for up to 10 years. At extremely low temperatures, the Water Bear's body can go from 85% water to just 3%, ensuring they are not ripped apart by the water in their bodies expanding during freezing. When re-hydrated, it can take as little as 4 minutes for the animal to bounce back from its near-death state. Natural selection has seemingly thought of every extreme environmental condition on earth; the harshest pressure (they can survive in close to vacuums), temperature, radiation (5,000gy of gamma rays compared to the lethal dose of 5-10gy for humans), dehydration and environmental toxins. Certain species can even survive in outer space! (slight sensationalism), and in my view they truly earn their title of extremophiles. Science has so much to learn from such a tiny animal, particularly the proteins they produce to protect their cells from apoptosis during dehydration. (this seems to be a theme of my blog now), and even if humankind never make inter-planetary colonisation a reality, the Tardigrade is an excellent candidate to be our intergalactic envoy.