transcription factor

No Payne No Gain

TEXT: Paul Flynn


Last year LIAM PAYNE had a conversation with Justin Bieber. He doesn’t usually do this sort of thing. There’s a shop Liam frequents in Los Angeles. Whenever he sees one of Will Smith’s kids or a Kardashian he feels too self-conscious to introduce himself. “There’s still that little boy inside of me,” he says. With Bieber, it was different.

Like each of the select bands who go through their boy-to-man rite of passage in full public glare, Liam at 23 is a disarming mix of confidence, knowledge and conviviality wrapped up in a frightened canary let out of its cage. Sometimes he’s the boy at the bus stop. Sometimes drops in reflexive anecdotes about his dealings with Donald Trump. No one understands Bieber’s experiences with quite the same clarity on quite the same timeframe as Liam and his four One Direction buddies.

“Obviously [Bieber]’s struggled a lot through the way the world looked upon him,” Liam says. “I don’t feel sorry for him,” he continues, “he’s great guy, inside there’s a really good heart. I said, look, the difference between me and you is that I had four different boys going through the same thing to look to. He didn’t have that.” Quite out of character, Liam Payne reached out a hand to his peer. “I said to him, listen, take my number and any time you want to have a chat, let me know because I’m here and I understand exactly what you’re going through and I understand your world.”

It was a lovely thing to do. “He needs somebody like that and in that position,” he qualifies, placing himself deferentially into the third person. It’s sweet for other reasons, too. In Bieber there is something of the idiosyncratic otherworldliness of a Michael Jackson figure. Liam Payne, a pretty, straight talking lad from Wolverhampton appears at first not to be that thing at all. “There is that in all of us.” he avers, meaning not only Bieber but his fellow One Direction alumnus Zayn Malik, Harry Styles, Niall Horan and Louis Tomlinson. “We all have this chaotic side to us. You know, they say that anger breeds passion. I think that’s the same with a lot of us, that we let things get chaotic very quickly. We’re used to chaos.”

Liam is sitting in a quiet antechamber above the photo studio where today’s cover story has been shot. He says he likes interviews and honours the assurance in a quietly riveting half hour before he’s whisked magically away. It’s Friday evening. Liam has been working out with millennial precision to make sure he’s at top physical condition should he be required to lose his shirt during the shoot. He’s whippet slight flesh, definition counts.

Six years ago, One Direction came third on the national TV talent show, the X Factor. 1D was an assembly-line operation pieced together audition stages. Boys that barely knew one another, slotted seamlessly together in the kind of multi-demographic hit their boss Simon CowelI so adept at plugging into the national grid each year. That year, Liam and his bandmates Niall and Louis looked like they’d been schooled at a premium boyband academy. Each sported variants of Bieber’s early slideover haircut. It was easy to imagine any of them taking a stool in Westlife or learning to breakdance for Take That, had they been born in another time and place. Within the trio there was a safe place in which teenage girls and boys could measure their sexuality, whilst tapping their toes. That wheel still turned. Flanked at either edge of the three were genuinely new angles for the British boyband model; Harry Styles, Cheshire’s own reality-age Mick Jagger and Zayn Malik, a practising Muslim from Bradford and nonpareil physical work of art to whom supermodels have since flocked. The five together hit enough familiarity and newness to open up a global fame haul not touched since the heady days of Duran Duran, Culture Club and Wham back in the 80s. During the summer of their astronomical American takeover there was a plausible touch of Beatle-mania. They felt like an England football team winning the World Cup. Their records have sold in North Korea.

Liam and the boys were the first band to taste that fame level in the age of social media, making their story simultaneously that of the boys next door and untouchable messiahs. There was something refreshingly undone about them. Their best songs, ‘What Makes You Beautiful’, ‘Little Things’, ‘Steal My Girl’, even the precociously titled ‘Best Song Ever’ are undeniable additions to the Great British pop cannon. Liam says the 1D song that he’d buy above all others is 'Once In A Lifetime’, the little known track from their 2014 album, Four. “That’s my favourite song. Very Coldplay-esque. I wanted it to be a single but they just wouldn’t have it. It was very relaxed the way we chose our records and made things. It was really simple.” Someone else did it.

When 1D lost their X Factor trophy to semi-hot handyman Matt Cardie and were beaten to the silver medal podium by classy Scouse songbird Rebecca Ferguson, Liam was 16. He had auditioned for the show pre­viously, at 14, as a kind of minipops Michael Bublé, Wolverhampton’s hitherto unseen swing angle. On his first induction to the X Factor factory, he was instructed by producers to go home and rethink his shtick as the last 24 were whittled down on TV. He says it attuned him to the hard knocks of rejection. Such was the omnipotence of the show back then Liam’s audition storyline was enough to grant him a local working men’s club career where he honed his skill and paid his dues.

“I did pubs and clubs.” he says. “When I was a kid, I literally played old people’s homes.” His one taste of what was to come arrived when the Wolverhampton Wanderers FC invited Liam to sing before kick-off at the Manchester United fixture to 34,000 fans in the terraces. In honour of his local team’s squad colours he sang Sam Sparro’s 'Black and Gold’. “It’s funny that that’s where we ended up, playing stadiums,” he says, with pleasing air of pride and bemusement. “It was funny being stood in the middle again and thinking back on that 16 year old boy stood in the middle of a football pitch. My dad said to me, this is going to be the toughest gig you’re ever going to play. Football fans do not want to hear little boy singing. They’re not interested. You heard jeering from the crowd. But I got applause at the end. And my dad said, that is the best thing you could’ve got out of today.”

Liam says he can’t remember much of his time in the X Factor house second time around bar the tears. He was recently delighted to see fellow housemate Page Richardson, the contestant Louis Walsh immortalised as looking 'like a little Lenny Henry’ on account of nothing but his colour, in a Harry Potter film (“the one where it’s Dumbledore’s army. He’s actually in the army, which is amazing. I’m absolutely obsessed with Harry Potter. Fucking love Harry Potter.”). He nods as I mention some of the other names he shared his first home away from Wolverhampton with. Katie Waissel, Diva Fever, Wagner. “There were a lot of different strange characters and lovely people through that show. It was very rushed and strange.”

On account of a childhood kidney condition, he had not even been drunk by the time he left home, Dick Whittington style, to live in a shared London house with a bunch of strangers maniacally chasing their fame dream in real time. “The famous line my dad said was. don’t come home until Christmas, meaning don’t get thrown off it before the final. And after I said goodbye to him that day. I never really went home again.”

When 1D lost, Liam turned to his dad with a “we made it this far” face. His fellow band-mates. he says, were in pieces. He remembers first Harry, then Louis, Niall and Zayn bursting into tears. “A cameraman came over and said 'can I get you boys for an interview?’ and I looked at all the boys crying, in their mum’s arms and I was like, 'look, I’ll do the interview’ because I was the only one who was alright and so I went off to side and did the after-camera interview for us. I just left them because I wanted them to have their moment and the cameras didn’t need to see them like that. There was a real atmosphere. This followed throughout our career a lot of the time.”

In Cowell’s dressing room later than same evening, 1D were told that they would be signed to his label, Syco regardless of their position on the show. “Simon took us up to his dressing room to tell us he was to sign us and Harry literally burst into tears he was so happy.” Emotions run high in boyband land. “He told us. I’m going to sign you. That was the moment. That’s where it all began.” The wheels of the juggernaut had begun to turn. “It was like a bomb went off”, he notes.

There was a pearl of wisdom shared by Cowell that stuck with Liam from that high-stakes evening. “The first thing he said to us after signing us from X Factor was 'look, there are no angels here.’ Which is so true.” What does Liam think Cowell meant by that? “That we’re all people. We all people here.” He doesn’t think it was an invocation of mistrust in music industry, the smoke and mirrors world of real life fame? “No, no, no. It was a moment in a conversation. He said 'look, there are no angels here and I know that you’re all going to make mistakes’. That’s what he was saying. Just get on with what the show is, do your bit. do your business, go to work and be real. That’s what that comment meant. Don’t stress about it, it’ll all turn out alright in the end.”

In that moment, it sounds like Liam Payne made a pact with himself go for it regardless, at the top tier, to claim his moment. “Everyone strives to be the person that they want to be.” he says. “I try too much sometimes, I think. I overstep the mark a little bit sometimes. That’s why I’m such a perfectionist. But sometimes I think you have to believe that are no angels.” The first One Direction single, 'What Makes You Beautiful’ was released in 2011, on September 11th.

The second half of 2016 was an eventful time for Liam Payne, presaged by his signing a solo record deal with Sinatra’s old imprint Capitol Records on July 21st.

While in 1D, he says all five boys dabbled on their own material. Because boybands never break up anymore, 1D are officially on sab­batical. Whether that translates as a bit of genial respite or full scale hatred for one another is a matter that’s been carefully blended into their tale with just enough leaks of a hint to either. Zayn, who had already fled 1D’s nest a year earlier, missing their victory lap worldwide stadium tour released his solo album Mind of Mine last spring, reinventing him­self as the Frank Ocean for Unilad readers. Niall played to his Irish card with a forgettable busker-ish ballad for the Christmas market very much carved from the mould of Ed Sheeran and seasonal John Lewis adverts. From the snippet of it we heard. Liam’s song sounded like his ascent to manhood, touting him as a moody, roustabout lover-man in something of Drake’s lineage, complete with street lyrical touches (while writing, a picture appears on Liam’s Instagram feed of him with the Canadian don though it’s not specified whether he’s working or partying with his hero)

Whenever Liam talks about the 1D boys he has the exact same dad-ish air of concern, care, amazement and slight separation from the operation that Daddy Barlow has with Take That. Oh, that’s the other thing Liam had kicked off the year with a new belle, The X Factor’s Queen of Our Hearts, Cheryl Tweedy.

Liam brings up Cheryl, of course he does. The two live in Surrey, out of the city. When I make a joke about him being Lord of the Manor, he says that his sister bought him a plaque to denote his Lordship for his last birthday, a joke that doubled when it turned out Cheryl had been bought a similar gift by Simon Cowell during her tenure on X Factor. “So we’re Lord and Lady, which is hilarious.” To British suburbia, this is of course precisely what they represent, a self-selected aristocracy in which we’ve all played a part in the honours system.

He says things with Cheryl are working out well, becoming temporarily misty-eyed. “This is the thing. In a non-cliché way, it’s weird waking up every day and literally living out your dream. You wake up in the most beautiful places. Obviously I have the most beautiful girlfriend if the whole world and she’s absolutely amazing. She’s been my drean girl since I was younger. She’s so ace.” They are used to companionship. They have Liam’s dog, Watson, a Great Dane. “If I’m ever having a problem or I ever get a bit angsty about something that’s happening in life then I take the dog out for a walk and there’s just unconditional love from him. Anyway, I don’t want to go too much into that. I’m not like a weird dog person.”

“She is a wonderful, wonderful person and it’s amazing to have someone who can relate to so much of things, someone who’s taken greater steps than me. Her solo career was amazing. She’s been in the industry for fourteen years now. She fully supports me. We’re super happy. I appreciate you didn’t ask about it. It’s a very personal, precious time for us. I’m still learning. I’m only 23.”

Because he is the youngest of three, Liam inherited the bed that his big sister’s had slept in at home in Wolverhampton. He tried to paint a wall blue to put his own stamp on the room, still shaded by bunny rabbit curtains into his teenage years, and ran out of paint before finishing. “It was a total tip.” he says of the last bedroom he lived in before fame. “That bed was so old. The last time I went back and sat on it I couldn’t believe it was the bed I used to sleep on. I often think about how I used to sit on the windowsill and just look at the stars and wonder what this was all for. And I often used to think, there must be more to life than this.”

I ask if his parents kept the room the same as when he left. “Well,” he says, interrupting the nostalgia with a little sharp reality, “I bought my par­ents a house so I haven’t actually been back to that room in a long time. I’d like to.” The experiences of 1D made five men very rich, very young.

Liam knows exactly his financial worth. “I do,” he says, letting out a nerv­ous laugh. I ask if I would blush if I saw his bank account. 'Honestly, it is a very scary thought.’ he says. “It is not something that we were given it’s something we worked our asses off for. The way we went to work every day and the way we travelled the world and the way we conducted our business, with great management at the time and greater minds, it turned out great for everybody. But it was a long five years.”

On the last night of the last 1D tour, management presented all four remaining members with a plaque festooned with little badges for every single gig they’d played since their first. “It was a sombre night.” says Payne, who has started becoming more emotionally transparent in front of other people this last year. “To see every show we’ve ever done on a plaque?” he says, raising eyes to the sky. “Again, everybody was in tears. And I’m quite good at holding it together but I have got a lot worse of late. Adverts and things mate me cry. I think I’m getting more emotional as time goes by, especially with everything that’s happening in my life at the moment. It’s a very emotional time and time to reflect on a lot of things and the person that I am to be. Do you know what I mean? If that makes sense?” It makes perfect sense.

Beneath the extraordinary life he has lived so far, outweighing every one of his personal, societal and geographic expectations, there’s a deeply admirable humility and candour to Liam Payne. On the subject of his forthcoming record: “l’ll tell you the truth. The dream was to be able to get signed and release an album. That is every musician who’s on Youtube’s dream today. I’ve got the opportunity to work with a really great label, Capitol. The people I work with are absolutely amazing and to get a record deal and be able to release the album that I want to release is the most amazing thing ever.” He has no idea how it will fare. “Even if this went tits up, sideways, it’d still be step one that I got here.”

Liam Payne never voted in a general election. “I’ve never been able to vote,” he explains, “because we’ve always been in different countries and I’ve never really understood it. I still feel like a 16 year old boy when it comes down to things like that and I wouldn’t know which way to go.” He steered clear of the EU referendum (“I kind of knew that we were going to Brexit. It was just a gambler’s feeling”) and doesn’t know how his parents voted in it.

Do you want to know his Donald Trump tale? Of course you do. 'Oh. here’s a story,“ he says, rubbing his hands. “Trump actually kicked us out of his hotel once.” It gets better. “You wouldn’t believe it. It was about [meeting] his daughter. He phoned up our manager and we were asleep. He said 'well, wake them up’ and I was like 'no’ and then he wouldn’t let us use the underground garage. Obviously in New York we can’t really go outside. New York is ruthless for us. So he was like, 'OK. then I don’t want you in my hotel’. So we had to leave.”

He’s seen a lot of life, has Liam. That he retains himself amid it’s spectacular credit to those around him and the man himself. “Now he’s President,” he says, perhaps for a moment reflecting on the opportunities life affords the most unusual candidates. “I just hope he doesn’t kick me out the country.” He’s laughing now. “I hope he lets me stay.”

Source: x

Live water mount of Hydra (left) capturing its Daphnia prey (right).

Fun Fact: Hydra are biologically immortal, meaning they appear not to age or die of old age.

Discovery of nano ‘footballs’

Research from the University of York has unearthed a ‘simply breathtaking’ discovery.

The work states that genes are controlled by ‘nano footballs’ – structures that look like footballs but are in fact 10 million times smaller than the average ball.

Professor Mark Leake, Chair of Biological Physics at the University of York, and who led the project said, ‘Our ability to see inside living cells, one molecule at a time, is simply breathtaking.

‘We had no idea that we would discover that transcription factors operated in this clustered way. The textbooks all suggested that single molecules were used to switch genes on and off, not these crazy nano footballs that we observed.’

Leake and his colleagues – supported by the Biotechnology and Biological Sciences Research Council, the University of Gothenburg and Chalmers University of Technology, Sweden – placed glowing probes on transcription factors, which are chemicals inside cells that control whether a gene is switched on or off. From this, it was determined that the transcription factors operate as a cluster of approximately seven to ten molecules.

The discovery could improve understanding about how genes operate and potentially provide more information on health problems associated with genetic disorders.

‘We found out that the size of these nano footballs is a remarkably close match to the gaps between DNA when it is scrunched up inside a cell,’ Leake added. ‘As the DNA inside a nucleus is really squeezed in, you get little gaps between separate strands of DNA which are like the mesh in a fishing net. The size of this mesh is really close to the size of the nano footballs we see.’

This, continued Leake, means that a nano football ‘can roll along segments of DNA but then hop to another nearby segment’, so it can find the specific gene it controls more quickly.

Reconstructing life at its beginning, cell by cell

After 13 rapid divisions a fertilized fly egg consists of about 6,000 cells. They all look alike under the microscope. However, each cell of a Drosophila melanogaster embryo already knows by then whether it is destined to become a neuron or a muscle cell – or part of the gut, the head, or the tail. Now, Nikolaus Rajewsky’s and Robert Zinzen’s teams at the Berlin Institute of Medical Systems Biology (BIMSB) of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) have analyzed the unique gene expression profiles of thousands of single cells and reassembled the embryo from these data using a new spatial mapping algorithm. The result is a virtual fly embryo showing exactly which genes are active where at this point in time. “It is basically a transcriptomic blueprint of early development,” says Robert Zinzen, head of the Systems Biology of Neural Tissue Differentiation Lab. Their paper appears as a First Release in the online issue of Science.

Keep reading


Transcription of DNA into RNA, enzymatic reactions, RNA, RNA degradation

  • Transcription
    1. Initiation: promoter recognition, closed complex, open complex.
      • Promoter:
        • Prokaryotic: ←upstream, -35 region, Pribnow box, transcription start site (TSS, +1), downstream→
        • Eukaryotic: ←upstream, several upstream elements, TATA box, initiator element containing TSS (+1), downstream→
        • The high A-T composition in promoters facilitate unwinding of DNA.
        • Template strand = antisense strand = (-) strand = noncoding strand = the DNA strand that serves as the template for transcription.
        • Nontemplate strand = sense strand = (+) strand = coding strand = the DNA strand having the same sequence as the transcribed RNA.
      • Binding to promoter:
        • Prokaryotic:
          • holoenzyme = core enzyme (polymerase activity) + σ-subunit (promoter and strand specificity).
          • binding first forms the closed complex, and then DNA opens up, forms the open complex.
        • Eukaryotic:
          • A whole bunch of transcription factors (TFs) involved in promoter recognition, binding, and openning up DNA.
          • TBP = Tata binding protein. TAF = TBP associated factor.
          • Phosphorylation of Pol II C-terminal domain (CTD) opens DNA up, forms the open complex.
        • Polymerase must transcribe using the correct template strand. The σ-factor (prokaryotes) and TFs (eukaryotes) tell the RNA polymerase to bind the coding strand, while using the template strand as the template.
    2. Elongation:
      • Polymerases:
        • Prokaryotes have just one.
        • Eukaryotes have three:
          • 1. RNA Pol I: makes rRNA (except the small 5S rRNA that resembles a tRNA in size).
          • 2. RNA Pol II: makes mRNA.
          • 3. RNA Pol III: makes tRNA (and 5S rRNA).
      • Incorporation of NTPs.
      • Prokaryotes lose σ-subunit. Eukaryotes lose TFs.
      • Topoisomerases relaxing supercoils ahead and behind the polymerase.
      • Transcription-coupled repair: RNA Pol II encounters DNA damage, backs up, TFIIH comes along, recruits repair enzymes. Defective TFIIH → faulty transcription-coupled repair → Xeroderma pigmentosum and Cockayne syndrome (skin sensitive to sunlight radiation in both diseases).
    3. Termination
      • Prokaryotic:
        • Intrinsic termination: GC hairpin (stalls polymerase) followed by poly U (slips off).
        • Rho-dependent termination: ρ protein catches up to polymerase when it stalls at the hairpin, and bumps it off.
      • Eukaryotic:
        • Termination consensus sequence reached (AAUAAA).
        • Polymerase released somewhere further downstream to the consensus sequence.
  • RNA
    • 1. RNA = ribonucleic acid, has 2’-OH.
    • 2. rRNA = ribosomal RNA
      • Most abundant (r for rampant).
      • Catalyzes peptide bond formation in the ribosome.
    • 3. mRNA = messenger RNA
      • Longest (m for massive).
      • Contains sequence of codons for translation.
      • RNA splicing
        • pre-mRNA need to be processed.
        • Introns = interfering sequences, cut out.
        • Exons = spliced together.
        • RNA splicing proceeds via a lariat intermediate, by the action of the spliceosome (snRNPs), introns released in lariat form.
        • Some RNA can self splice.
    • 4. tRNA = transfer RNA
      • Smallest (t for tiny).
      • Contains anticodon.
      • Shuttles the correct amino acid to the correct codon during translation.
    • 5. snRNPs (snurps) = RNA + protein, involved in RNA splicing.
  • RNA degradation
    • RNases degrade RNA.
    • Post-transcriptional modifications protect RNA from degradation (5’ cap and polyA tail)
    • 2’-O-methylation prevents that position from attacking the RNA backbone.

It’s not just fish hips and cat thumbs that are the result of small changes in genetic control switches. David Kingsley has also discovered a few human traits that work in the same way, with the most immediately obvious being skin and hair colour. A few years back, he and his team discovered that the DNA around a gene called Kitlg, found in many animals including both sticklebacks and humans, seemed to be chock-full of control switches. The protein encoded by Kitlg (known as Kit ligand) is a biological multi-tasker, helping to make blood, sperm and cells packed full of the dark pigment melanin. It’s this molecule that determines your coloration. More melanin and you’ll be darker, less and you’ll be lighter. Kingsley and his team discovered that playing with these switches in sticklebacks changed their coloration, making them darker or lighter depending on which ones were missing. So they took the same DNA region from humans and broke it down into pieces, testing each one to find out when and where it was active.

Sure enough, they tracked down one specific control switch that could turn on the gene only in skin and hair. Then when they looked at the DNA sequence of this switch in West Africans and white Europeans, they noticed a consistent difference in a region more than 300,000 letters (300 kilobases) away from Kitlg. Not as far as the distance between Sonic Hedgehog and its limb control switch, but still a long way off. One single letter was switched: an A in the Africans, a G in Europeans. Just one.

Next, they tested whether this change affected how well the switch could turn on Kitlg, by looking at the two different versions in skin cells grown in the lab. They discovered that it wasn’t as simple as an on/off (or rather, black/white) switch. Instead, the version in Europeans wasn’t quite as effective at activating the gene as the African version was. A quick calculation in their paper suggests that having two copies of Kitlg with the European switch makes a person’s skin around six or seven shades lighter than someone with two West African versions. Because you have two copies of every gene – one from Mum and one from Dad – the effects of the switches will be more apparent if they are both the same, while having one of each will give a colour somewhere in the middle.

However, there are around 30 shades between a typical Nigerian’s dark skin and a pale European complexion, so the difference in the Kitlg switch only explains part of our skin colour, rather than the whole thing. David suspects that there are probably other similar genes and switches out there that add up to give each person their particular hue. But even so, just a single letter can make a big difference to what you look like. This is true of hair colour as well as skin. In 2014 Kingsley and his team published another paper showing that European blondes have a single letter difference in a control switch around 350,000 DNA letters (350 kilobases) away from the Kitlg gene, compared to dark-haired people. Again, it’s a tiny change miles away from the gene, but it has a big impact. This subtle alteration in blondes means that a transcription factor protein called Lef can’t stick quite as well to the DNA of the control switch, so it’s not as effective at turning on Kitlg activity. It’s not on/off, but it’s enough to significantly cut down the melanin production in hair cells, and make them fair.

Growing up in the 1980s, I would often hear jokes about blondes being stupid – and as a brunette (to my shame) I would often repeat them. I now know better, but many people apparently don’t. In a news article about his hair colour research, Kingsley attacked this long-held stereotype, saying, ‘It’s clear that this hair colour change is occurring through a regulatory mechanism that operates only in the hair. This isn’t something that also affects other traits, like intelligence or personality. The change that causes blonde hair is, literally, only skin deep.’ Blonde jokes aside, his work on coloration has more profound implications. As I’m writing this chapter, the United States is fracturing under the stress of racial tension following several high-profile incidents of white police officers killing unarmed black people, and a horrific racist shooting in a church. Countless numbers have been unfairly judged, oppressed or killed throughout history because of the colour of their skin, yet it boils down to little more than a handful of DNA letters in a few genetic switches. For a species named after our intelligence – Homo sapiens translates as ‘man who knows’ – we really are very stupid at times.“

welcome to high school!! it might seem scary at first, but you’ll soon fall into routine and find that it’s not as bad as everyone makes it out to be. here’s the advice i’d give to incoming freshmen.

  1. get involved in things!! not only is joining clubs a great way to enjoy your passions, but they’ll also help you make friends, and get you out of the house. sports, band, yearbook, debate, art club— whatever floats your boat!! don’t be afraid of the commitment, and participate in whatever you’re a part of. 
  2. everyone else is in the same boat as you. you’re not alone. all the other freshmen feel a little lost and alone too, so stick together and make some friends. don’t be afraid to strike up conversations and talk to other people!!
  3. stay organized! i know everyone says it, but seriously. get binders and dividers, use your planner, and stay on top of everything you need to do!! by the time midterms and finals roll around, you’ll thank yourself, and being organized now will give you a head start on the rest of high school. as long as you don’t use an ‘everything folder’ and you’re probably fine tbh
  4. get a sturdy backpack! you’re probably going to end up carrying it more than in middle school, and carting it around school rather than leaving it in your locker. pick something that’s comfortable to carry, supportive of your back, and will last you a good amount of time. 
  5. don’t be afraid to talk to upperclassmen. they know their way around the school— geographically and in terms of classes— and most of them aren’t that scary. they may call you fresh meat, but most of the time it’s a joke, and not to intimidate you. talk to them and you’ll often find good advice and someone who can help you out!!
  6. take electives. freshman year is a great time to explore what your school offers, and your classes will probably be easier than in any other year!! so explore the art, music, graphic design, speech, or creative writing classes, and enjoy yourself a little :D
  7. freshman year matters!!!! don’t fall into the trap of thinking that your grades this year don’t count for anything, because they’ll show up on your transcript and be factored into your GPA. start good habits now, and do your best in all your classes, and it’ll help in the long run!!

(this post was requested by anon!! see my other posts here and request a post here :D)

Oncogenes and tumour suppressors are mutation targets promoting the onset and maintenance of cancer. Oncogenic mutations result in gain-of-function and deregulation of the function of the oncoprotein that they encode. Tumour suppressors act to run quality checking of DNA, keep cell cycle checkpoints, and shut down mitogenic signals; mutations in genes encoding tumour suppressors can lead to absence of these checks and give activated oncoproteins the chance to run riot in a cell. Co-incidence of mutations in oncogenes and tumour suppressor genes potentially leads to cancer.


Ras is a small G protein involved in a whole host of cellular functions. Mutation of Ras at a functional site can lead to a pleiotropic phenotype. Oncogenic Ras causes inappropriate signalling through its three pathways: MAPK, PI3K, and RalGEF. Signalling through the PI3K activates antiapoptotic Akt (PKB), which acts to promote cell survival. Signalling through RalGEF causes cell motility by formation of filopodia (Cdc42) and lamellipodia (Rac), which may be associated with metastasis. Signalling through MAPK actually causes the expression of some Ras signalling inhibitors (Sproutys, SPREDs, GAPs) which shuts down the signal in normal cells.

Myc is a transcription factor with more than 8000 transcription targets. Deregulated Myc leads to cell proliferation, but does not block apoptosis. Thus, it leads to a modest amount of growth before it is eradicated by apoptosis. Inhibition of apoptosis by antiapoptotic Bcl-xL is tumourigenic in cells expressing Myc highly. Additionally, Myc is thought to contribute to the tumour microenvironment, immune evasion, and inhibition of differentiation.

Ras and Myc work together by combining their abilities. Myc promotes cell proliferation and disfavours differentiation, and Ras inhibits apoptosis. The combination of the two means that cells are allowed to proliferate without triggering apoptosis. Ras actually activates Myc in normal cells - but in normal cells, activation is transient. Ras stabilises Myc by phosphorylation on S62 through MEK signalling, but also promotes its degradation by phosphorylation on T58 through PI3K signalling. The result is transient activation of Myc by Ras. Mutations which ultimately block phosphorylation at T58 will switch activation by Ras from a transient to a constitutive response.

Tumour suppressors

p53 is the so-called guardian of the genome. High Myc and oncogenic Ras cause stabilisation and activation of p53. p53 gets two bites at the cherry to combat the inheritance of damaged genomes: at the point of DNA damage, p53 arrests the cell until the DNA is repaired. p53 decides whether the cell enters senescence or apoptosis - its own state of post-translational modifications and the genomic context of its target genes (p53 is also a TF) on the genome in that particular cell both play a role in which way the scale tips. In this way, p53’s second bite of the cherry is the selection of apoptosis in cells whose DNA is damaged beyond repair.

Rb is the keeper of the G1/S checkpoint. Loss of both copies of the Rb gene leads to retinoblastoma. Familial retinoblastoma predisposes heterozygotes with a heightened risk of retinoblastoma by loss of heterozygosity - loss of their only functional copy. This can occur by mutation, but also by mitotic recombination, gene conversion, and nondisjunction. Cells null for Rb can still enter G0 phase, as p107 and p130 share some redundant functions with Rb.

NF1 displays the phenomenon of haploinsufficiency. Nf1-/- Schwann cells can be complemented for the wild-type by Nf1+/+ mast cells, but not Nf1+/- mast cells. The former gives the wild-type; the latter causes neurofibromas.

VHL suppresses the hypoxic response in normoxia by mediating the ubiquitin-associated degradation of HIF-1α in normoxia. Loss of VHL leads to a hypoxic response no matter the oxygen level.

Further reading:

  • Hanahan, D.; Weinberg, R.A. 2011. “Hallmarks of cancer: The next generation.” Cell 144:646-674.
  • Lowe, S.W.; Cepero, E.; Evan, G. 2004. “Intrinsic tumour suppression.” Nature 432:307-315.
  • Pylayeva-Gupta, Y.; Grabocka, E.; Bar-Sagi, D. 2011. “RAS oncogenes: Weaving a tumorigenic web.” Nature Reviews Cancer 11:761-774.
  • Soucek, L.; Evan, G.I. 2010. “The ups and downs of Myc biology.” Current Opinion in Genetics and Development 20:91-95.
  • Vousden, K.H.; Prives, C.; 2009. “Blinded by the light: The growing complexity of p53.” Cell 137:413-431.
  • Burkhart, D.L.; Sage, J. 2008. “Cellular mechanisms of tumour suppression by the retinoblastoma gene.” Nature Reviews Cancer 8:671-682.
Mutating the switches

Gene transcription is complicated. The process of making RNA copies of stretches of DNA requires a large number of proteins attaching to and interacting with the genetic material to get the ball rolling. These proteins attach to the DNA at promoter sites near the start of genes, and other more distant control regions called enhancers. Both of these areas are known as regulatory regions, or genetic switches, and are used to turn gene expression on and off to meet the needs of the cell.

According to a couple recent studies published in Nature, these collections of proteins that gather around promoters and enhancers make these genetic switches more prone to lasting mutation than the surrounding DNA by blocking the action of the cell’s repair crew.

Mutations happen all the time as you are exposed to carcinogens throughout your day. For example, just spending an hour in the sun causes about 80,000 mutations in each cell. Fortunately, your cells come with an expert DNA repair team that runs around the nucleus fixing damage as fast as it happens. Occasionally, they miss a spot, and the mutation sticks, affecting all future generations of that cell. If the mutation is in a critical gene or control area, the cell can start to divide uncontrollably, resulting in cancer.

When access to the DNA is blocked by proteins gathering to turn a gene on or off, the repair crew can’t get in to fix damage caused by factors like UV radiation. Both groups of researchers analyzed mutation rates along strands of DNA from cancer cells, and found that some of the highest mutation rates occurred right in the middle of these regulatory regions. This means that mutations aren’t being fixed by the repair team nearly as often as they should.

This is important in understanding how cancers form initially. Mutations in the regulatory regions can cause the on-off switches to lose their function, and genes that should be tightly controlled by the cell could be either on or off all the time. At this point of the research, it isn’t clear what we might be able to do about these “protected” mutations, but every bit of knowledge about how cancer gets started could help us find better ways of treating and preventing this horrible disease.

References and further reading

Hard-to-reach repairs, Ekta Khurana, Nature, 4/14/16, p 181

Differential DNA Repair underlies mutation hotspots at active promoters in cancer genomes,Dilmi Perara et al, Nature, 4/14/16, p 259

Nucleotide excision repair is impaired by binding of transcription factors to DNA,Radhakrishan Sabarinathan et al, Nature, 4/14/16, p 264

DNA Damage & Repair: Mechanisms for Maintaining DNA Integrity, Suzanne Clancy, Scitable,2008

Image credit: Wikimedia user Forluvoft, public domain

This is how super smart octopuses are

The cephalopod’s genome reveals how the creatures evolved intelligence to rival the brightest vertebrates.

We humans think we’re so fancy with our opposable thumbs and capacity for complex thought. But imagine life as an octopus … camera-like eyes, camouflage tricks worthy of Harry Potter, and not two but eight arms – that happen to be decked out with suckers that possess the sense of taste. And not only that, but those arms? They can execute cognitive tasks even when dismembered.

And on top of all that razzmatazz, octocpuses (yes, “octopuses”) have brains clever enough to navigate super complicated mazes and open jars filled with treats.

The octopus is like no other creature on this planet. How did these incredible animals evolve so spectacularly from their mollusk brethren? Scientists have now analyzed the DNA sequence of the California two-spot octopus (Octopus bimaculoides) and found an unusually large genome. It helps explain a lot.

“It’s the first sequenced genome from something like an alien,” says neurobiologist Clifton Ragsdale of the University of Chicago in Illinois, who co-led the genetic analysis, along with researchers from the University of Chicago, the University of California, Berkeley, the University of Heidelberg in Germany and the Okinawa Institute of Science and Technology in Japan.

“It’s important for us to know the genome, because it gives us insights into how the sophisticated cognitive skills of octopuses evolved,” says neurobiologist Benny Hochner who has studied octopus neurophysiology for 20 years.

As it turns out, the octopus genome is almost as large as a human’s and actually contains more protein-coding genes: 33,000, compared with fewer than 25,000 in humans.

Mostly this bonus comes from the expansion of a few specific gene families, Ragsdale says.

One of the most remarkable gene groups is the protocadherins, which regulate the development of neurons and the short-range interactions between them. The octopus has 168 of these genes – more than twice as many as mammals. This resonates with the creature’s unusually large brain and the organ’s even-stranger anatomy. Of the octopus’s half a billion neurons — six times the number in a mouse – two-thirds spill out from its head through its arms, without the involvement of long-range fibers such as those in vertebrate spinal cords.

A gene family that is involved in development, the zinc-finger transcription factors, is also highly expanded in octopuses. At around 1,800 genes, it is the second-largest gene family to be discovered in an animal, after the elephant’s 2,000 olfactory-receptor genes.

Not surprisingly, the sequencing also revealed hundreds of other genes specific to the octopus and highly expressed in particular tissues. For example, the suckers express a unique set of genes that are similar to those that encode receptors for the neurotransmitter acetylcholine. This may be what gives the octopus the spectacular characteristic of being able to taste with its suckers.

The researchers identified six genes for the skin proteins known as reflections. As their names suggests, these alter the way light reflects from the octopus allowing for the appearance of different colors, one of the tricks an octopus uses – along with changing its texture, pattern or brightness – in their mind-blowing ability to camouflage.

When considering the creature’s extraordinary learning and memory capabilities, electrophysiologists had predicted that the genome might contain systems that allow tissues to rapidly modify proteins to change their function; this was also proven to be the case.

The octopus’s position in the Mollusca phylum illustrates evolution at its most spectacular, Hochner says.

“Very simple mollusks like the clam – they just sit in the mud, filtering food,“ he observes. "And then we have the magnificent octopus, which left its shell and developed the most-elaborate behaviors in water.”

DNA transcription

snRNA and nuclear proteins form snRNP’s [pronounced like snurps] that join protein complexes to form the complex molecular machine called splicisomes which remove introns from transcribed Pre-mRNA

Transcription factors bind to a region of the DNA called the promoter, which identifies the start of the gene, which strand is to be copied, and the direction in witch it is copied.

RNA polyemerase then binds to the transcription factors and promoters

(in prokaryotes there are no transcription factors so RNA polymerase binds directly to the promoter)

RNA polymerase unwinds DNA then aranges the complimentary nucleotides 


Then transcription stops:

in prokaryotes there is a termination sequence in the DNA that indicates where it will stop

In eukaryotes transcription stops after the polyadenylation signal

Our closest wormy cousins: About 70% of our genes trace their ancestry back to the acorn worm

A team from the Okinawa Institute of Science and Technology Graduate University (OIST) and its collaborators has sequenced the genomes of two species of small water creatures called acorn worms and showed that we share more genes with them than we do with many other animals, establishing them as our distant cousins.

The study found that 8,600 families of genes are shared across deuterostomes, a large animal grouping that includes a variety of organisms, ranging from acorn worms to star fishes, from frogs to dogs, to humans. This means that approximately 70% of our genes trace their ancestry back to the original deuterostome. By comparing the genomes of acorn worms to other animals, OIST scientists inferred the presence of these genes in the common ancestor of all deuterostomes, an extinct animal that lived half a billion years ago. This research shows that the pharyngeal gene cluster is unique to the deuterostomes and it could be linked to the development of the pharynx, the region that links the mouth and nose to the esophagus in humans. These findings were published in Nature, summarizing an international collaboration between OIST researchers and teams from the US, UK, Japan, Taiwan and Canada.

Around 550 million years ago, a great variety of animals burst onto the world in an event known as the Cambrian explosion. This evolutionary radiation revealed several new animal body plans, and changed life on Earth forever, as complex animals with specialized guts and behavioural features emerged. Thanks to the genome sequencing of multiple contemporary animals of the deuterostome group, we can go back in time to unveil aspects of the long-lost ancestor of this diverse group of animals.

Acorn worms are marine creatures that live on the ocean floor and feed by filtering a steady flow of sea water through slits in the region of their gut between mouth and esophagus. These slits are distantly related to the gills of fish, and represent a critical innovation in evolution not shared with animals like flies or earthworms. Since acorn worms occupy such a critical evolutionary position relative to humans the researchers sequenced two distantly related acorn worm species, Ptychodera flava, collected in Hawaii, and Saccoglossus kowalevskii, from the Atlantic Ocean. “Their genomes are necessary to fill the gap in our understanding of the genes shared by the common ancestor of all deuterostomes,” explains Dr Oleg Simakov, lead author of this study.

Indeed, beyond sequencing these two organisms, the team was also interested in identifying ancient gene families that were already present in the deuterostome ancestor. The team compared the genomes of the two acorn worms with the genomes of 32 diverse animals and found that about 8,600 families of genes are homologous, that is, evolutionarily-related, across all deuterostomes and so are confidently inferred to have been present also in the genome of their deuterostome ancestor. Human arms, birds’ wings, cats’ paws and the whales’ flippers are classical examples of homology, because they all derive from the limbs of a common ancestor. As with anatomical structures, genes homology is defined in terms of shared ancestry. Because of later gene duplications and other processes, these 8,600 homologous genes correspond to at least 14,000 genes, or approximately 70%, of the current human genome.

The study also identified clusters of genes that are close together in acorn worm genomes and in the genomes of humans and other vertebrates. The ancient proximity of these gene clusters, preserved over half a billion years, suggests that the genes may function as a unit. One gene cluster connected with the development of the pharynx in vertebrates and acorn worms is particularly interesting. It is shared by all deuterostomes, but not present in non-deuterostome animals such as insects, octopuses, earthworms and flatworms. The pharynx of acorn worms and other animals functions to filter food and to guide it to the digestive system. In humans, this cluster is active in the formation of the thyroid glands and the pharynx. Scientists suggest there is a connection between the function of the modern thyroid and the filter feeding mechanism of acorn worms. This pharyngeal gene cluster contains six genes ordered in a common pattern in all deuterostomes and includes the genes for four proteins that are critical transcriptional regulators that control activation of numerous other genes. Genes ordered in the same way and located next to each other in the chromosomal DNA are linked and transferred together from one generation to the next. Interestingly, not only the DNA that codes for these transcription factor genes is shared among the deuterostomes, but also some of the DNA pieces that are used as binding sites for the transcription factors are conserved among these animals.

“Our analysis of the acorn worm genomes provides a glimpse into our Cambrian ancestors’ complexity and supplies support for the ancient link between the pharyngeal development and the filter feeding life style that ultimately contributed to our evolution,” explains Dr Simakov.

Recently, the OIST team also sequenced the genomes of the octopus and the coral Porites australiensis.

Image: This is a juvenile of Saccoglossus kowalevskii with one of the transcription factors expressed in the pharyngeal region (highlighted in blue).

Credit: Andrew Gillis

mcknighty9  asked:

Teach me a zoologist lesson!

I would like to introduce you to Oikopleura

Not only does it have a smashing name, it is one of my favourite animals (despite looking like something from an alien movie)

It is a master predator of the tiniest of plankton, down to nanoplankton (that is, bacterial plankton). Every four hours, it builds itself a complex house (house is the correct scientific terminology) out of a gelatinous material. The house has meshes of varying thicknesses, one to keep out big particles that it can’t eat, and one to filter out smaller particles, which it does eat, carried to it’s stomach along mucus threads. Swimming like a tadpole, it pushes it’s house through the water column, filtering out it’s dinner as it goes (like this)

After about 4 hours, it sheds it’s house (it’s large filter will be clogged by that stage) and builds a new one. The old house sinks to the bottom of the sea as ‘marine snow’ and eventually collects as a marine ooze at the bottom of the sea floor, along with other biological droppings, and organic matter. Together, Oikopeurids contribute hugely to carbon sequestration on the sea floor.

Another cool think about Oikopleura, is that it is more related to you or I than you might think. Oikopleura is a Tunicate, the Subphylum more commonly known as Ascidians, or more common still, the Sea Squirts (see below)

Sea squirts lead a simple life, sitting in one spot, filtering seawater for food out of one opening, and expelling that water out of the other. However these primitive jelly looking things are more related to us, to your cat, your lizard, that bird, a fish etc., much more so than molluscs, arthropods, jellyfish - pretty much any invertebrate is. 

Sea Squirts are Chordates. Yes, you heard right, that is our phylum, the phylum of the vertebrates. Though their adult stage looks alien, their larval stage, is much more familiar

Their tadpole like larvae are free swimming. Whilst they don’t have a spine per se, they do have a notochord, a flexible cartilage like rod that runs along their body and post-anal tail, a kind of primitive spine predecessor that all vertebrates possess when we develop as embryos. Tail muscles attach to the notochord, much as tadpole tail muscles attach to a vertebral column, and allows the larvae to swim in that same undulating fashion. They also possess a number of characteristic chordate features - a hollow dorsal nerve cord, pharyngeal slits (so, gill slits essentially. We still even have them as early embryos), an endostyle (a gland that produces mucous and deals with iodine metabolism. It is the predecessor to our thyroid gland) and a post anal tail. 

Sea squirt larvae, once they hatch, swim around looking for a place to settle. When they find a nice looking spot, they stick themselves to the rock, and undergo metamorphosis, changing to their more simpler adult looking form. The genetic pathways, transcription factors, and other proteins that are active during the formation of the adult sea squirt heart and pharynx remain relatively unchanged during the embryonic development of those areas in vertebrates, which of course includes us (these ancient pathways are the focus in modern heart developmental biology, very relevant to tackling congenital heart defects). 

However, Oikopleura is different. It belongs to a group of Tunicates known as the Larvaceae, a group characterised by their retention of their larval form when they mature as adults, i.e no metamorphosis. This is known as neoteny, or pedomorphosis, when an individual can become sexually mature whilst retaining their juvenile form. Another example of this would be the Axolotls, who as adults, retain juvenile features such as gills, and don’t undergo full metamorphosis to an adult, semi-terrestrial salamander like form. And thus, Oikopleura lives out it’s adult life, retaining a larval ascidian body. 

Now here’s where it gets interesting. There is a theory that suggests that the first predecessors of the vertebrates, i.e. the predecessors to the first “fish” may  have been a neotenous tunicate, like Oikopleura. It would have had all the basic requirements and features for an ancient chordate and vertebrate predecessor, and by investing in a more active swimming lifestyle, it is not hard to see it evolving a more sophisticated pharynx for filter feeding and a more muscular hydrodynamic body for swimming, as in the earliest true chordate fossils, our ancestors from ~520 MILLION years ago, like Pikaia

or what is coined sometimes as the first “fish”, Haikouicthyes

So, TL:DR - Something very like the tiny Oikopleura may have been the ancestor to all vertebrates!!