Archive | All Posts RSS for this section

Drugs to make you smart

For as long as it has existed, the human race has strived to make itself better, to improve upon its natural ability and to push its boundaries. The Olympic games display impressive feats of human physical endurance, strength and skill. The Guinness book of world records celebrates some of the more ‘niche’ (yet no less impressive) human abilities, such as holding 43 snails on a face at once and squirting milk over impressive distances from an eyeball. These may not be particularly useful skills to have, but the collection of records in the Guinness book is still a demonstration of how we endeavour for success, to improve, and to be the best.

So what about our brains? Can we make them better, faster, smarter?

There are a group of drugs known as ‘Nootropics,’ or ‘Cognitive Enhancers’ that are used for just this purpose. These drugs act by changing the regulation of signalling systems within the brain – that is, they alter how brain cells communicate with each other, thereby subtly altering brain function. A cognitive enhancer aims to improve cognition – this is the brain’s ability to think, make decisions, learn, remember and solve problems. All are essential abilities for living independently, holding down a job, and succeeding at school.

SteroidBrain1

Various cognitive enhancers have been around for decades, and new ones are being developed all the time. However, these drugs are created with an aim to treating psychiatric and neurological problems, where poor cognition is a symptom or a side effect of the illness.  But do they work on healthy brains? Can we use drugs to push our cognitive abilities above and beyond our usual boundaries?

Can we make ourselves cleverer – *ahem* – I mean, more clever?

Well, it may be possible, although it’s not all that clear, and definitely not that simple. The use of cognitive enhancers in a healthy population is a relatively new consideration, so research into the effect of these drugs is very much in its early stages, and there is almost no data on the long-term effects of regularly taking such enhancers.

It’s also important to bear in mind that there is not one ‘wonder pill’ that can make someone smarter. Rather, there are many many different drugs that affect slightly different, and overlapping systems in the brain. Each one may therefore improve different and particular elements of cognition, which in turn means an individual is more able to learn, and as a result will be smarter. For example, different drugs will improve attention, others will affect memory, and others will increase alertness. By taking a cognitive enhancer, you will not suddenly be able to answer all of the questions on University Challenge.

So here is a summary of some of the most common cognitive enhancers currently being used:

ATTENTION (Ritalin/Atomexitine)

One of the illnesses that is most commonly treated with cognitive enhancers is ADHD (attention deficit hyperactivity disorder), which is characterised by a short attention span, hyperactivity and impulsiveness. Therefore cognitive enhancing drugs are thought to be a useful treatment. Two of the most common drugs used for ADHD are Ritalin (Methyphenidate) and Atomexitine.

Ritalin and Atomoxetine both increase noradrenaline and dopamine in the brain. Noradrenaline and dopamine are chemicals that send signals between brain cells, and are therefore known as ‘neurotransmitters.’ In ADHD, there is a reduction of both of these neurotransmitters, suggesting that communication within the brain is not efficient. By increasing the level of these neurotransmitters, Ritalin and Atomoxetine improve communication between brain cells, resulting in better alertness and attention.

So what about in a healthy individual without ADHD? Can these drugs further enhance cognition above and beyond what can be achieved with hard work alone? Many people believe so – ADHD-associated drugs are commonly found on university campuses, particularly in the USA when they have been illegally purchased by desperate students trying to improve their exam performance. But does it work?

The answer isn’t exactly clear. Several studies have indicated that taking Ritalin and Atomexitine can be beneficial in healthy adults – they can increase accuracy and performance on various cognitive-dependent tasks that require good attention and memory to perform well. But the size of the effect seems to be fairly modest, and seems to depend on the individual’s natural ability in the first place – those who had poor attention and memory to begin with saw an improvement in their performance after taking Ritalin, but there was no benefit for those who already performed well. Another dopamine enhancer, Bromocriptine (used for the treatment of Parkinson’s disease) actually lowered the performance of individuals who had initially performed well.

 WonderPill1

MEMORY (Aricept)

Cognitive enhancing drugs are also commonly used in those suffering from neurodegenerative diseases, such as Alzheimer’s or Parkinson’s disease. Both affect cognition and memory, and while there is no cure for either condition, cognitive enhancing drugs may delay or slow down the progression of the cognitive symptoms. Aricept (Donepezil) is commonly used for Alzheimer’s disease. It increases the levels of another neurotransmitter – acetylcholine – by stopping it being broken down and recycled in the brain

The majority of people experience and complain of a bad memory as they get older, so a memory-enhancing drug such as Aricept is going to be of interest to many people, not just those suffering with dementia. As such, research has begun to investigate how Aricept may affect healthy individuals. It has been found to enhance pilot performance after flight simulation training, although a review of multiple studies looking at Aricept found that evidence for its ability to enhance memory was unconvincing, with several studies finding no effect or even an impairment on cognitive ability following treatment.

ALERTNESS (Modafinil)

Modafinil (Provafil) is a treatment for narcolepsy and sleep apnea, and enhances cognition by increasing alertness and wakefulness. Apparently it is commonly used by some individuals in high-stress professions, or those that require long hours and shift work to help them stay awake,  such as doctors, military personnel, and academics. A study of British universities indicated that its use is pretty high among the undergraduate population too, and in 2013 described it as the ‘drug du jour’ to aid studying, despite being a prescription-only medication. The exact way that Modafinil affects the brain isn’t fully understood – it is thought that it may alter similar systems as Ritalin and Atomexitine, but it has also been associated with multiple other neurotransmitters and systems.

Modafinil has been shown to improve cognitive function in male volunteers by enhancing alertness and attention paid to the tasks they were given, and by inhibiting quick, impulsive responses. The volunteers also reported feeling more alert and energetic after taking the drug. However, other studies have found that similar to the ADHD drugs, Modafinil has a greater effect on those with a poor initial performance, and may be of limited use to those with a high cognitive ability.

Universitychallengedrugs1

Overall, there is some tentative evidence that cognitive enhancing drugs typically used for neurological problems could have some benefit in the healthy population. So what should stop you from grabbing a big ol’ box of pills to improve your performance at school or work? Well, lots of things, actually – here’s just a few:

  • A big deal is that no one knows the long term effects of taking any of these substances – the majority of studies investigate the effects of a single dose or treatment over just a few weeks.
  • It is important to also bear in mind that these drugs are likely to have undesirable side effects. When they are used in people with a neurological disease, it has been thought that the therapeutic effect of the drug outweighs the discomfort of the side effects. As the current evidence points to very modest effects in healthy people, the balance between the benefit and the risks may no longer be favourable.
  • It isn’t really understood how they work in healthy people, and it is different for everyone. Most of the studies I came across while researching this post pointed out that the effects of cognitive enhancers were very variable between different people. This may be down to an individual’s brain chemistry, gender or their genetics, but currently it isn’t possible to predict how or if a cognitive enhancer will work in any one person.
  • There’s a big ethical debate about whether the use of cognitive enhancers is ok. Is it cheating? How different is it to using caffeine? Would people feel coerced or pressured to take them in order to ‘keep up?’ Does it undermine the value of hard work?

I don’t know the answers to the ethical questions, and the argument is strong for both sides. Nevertheless, the use of cognitive enhancers is an interesting and divisive debate, and looks to be a growing field of research. However, the current consensus appears to be that these may be useful tools in the future for healthy individuals, but at the moment their benefits and effects are questionable.

Personally, I’m happy to continue to celebrate if/when I manage to answer just a single question on that darn University Challenge.

The Biocheminist.

Cake on the Brain

I love cake.

I mean, I really love cake. I exist in a constant battle between my desire for its delicious spongy goodness, and for maintaining a healthy BMI.

So of course, when considering what I would write about for my next blog post, cake was on my mind.

On my mind? Cake on my mind – that’s cake on the brain – that’s cake and neuroscience! Hurrah! I can write about cake!

It turned out that this was easier said than done. A quick google of ‘brain’ and ‘cake’ turned up a huge range of impressively brain-shaped desserts, but that wasn’t quite what I was after. So I turned to a database of scientific publications – a tool I typically use during my working day with precise and sensible search parameters to discover the latest work on a very specific topic. Not this time! I repeated my ‘cake’ and ‘brain’ search, and here are three things that I found:

 

  1. Oreos are practically Cocaine

Well, sort of. But not really. Oreos aren’t my delicious treat of choice, but it turns out that rats are pretty keen on them. A study identified which rats had a strong preference for Oreos and those that didn’t. They then compared how much cocaine either group of rats gave to themselves.

Now, rats that take cocaine aren’t dropped into a seedy nightclub, and don’t have teeny tiny credit cards or rolled up notes. Instead, a small tube (cannula) is implanted into their brain and is attached to a small pump. Whenever the rat presses a lever, this pump releases a controlled dose of cocaine through the tube and into their brain. The rats rather like this, and will learn that pressing the lever = getting high.

It turns out that the rats that loved the Oreos were also pretty darn keen on the coke. While both groups of rats learnt to press the lever, the Oreo-rats were slower to stop pressing it when the cocaine reward was stopped, and were much more enthusiastic in their pressing when the drug was reinstated. The study also found that presenting the rats with an Oreo before their stint in the coke-box temporarily boosted their lever pressing.

There was no such effect when rats were given rice cakes instead of biscuits (sorry, my American friends – ‘cookies’).

Oreo cartoon1

This suggests that Oreos (or any other delicious treat) are likely to work on the same pathways in our brains as drugs do – namely, those associated with motivation and reward. When we eat something delicious, we feel good due to the activation of ‘reward pathways’ in our brain – this feeling reinforces that behaviour so we are likely to do it again to get back that good feeling. Drugs hijack the same pathways. So when rats have a strong preference for Oreos, they may be more sensitive to how rewarding they are. This then makes them vulnerable to doing other things that will give a similar rewarding feeling. Such as cocaine.

It’s important to bear in mind, that although drugs and Oreos roughly use the same pathways of reward and motivation in our brains, they have vastly different effects on cells, addiction and health.

Take cake, not coke.

 

  1. Having that ice cream now will ruin your dessert.

…At least how much you enjoy it. In the previous section, I mentioned the brain’s reward pathway. Part of this pathway is regulated by Dopamine – a chemical released in the brain that transmits signals between cells (A.K.A a Neurotransmitter). Increased Dopamine signalling in the brain typically means something good has happened and you are being rewarded for it with some good feelings. So in the previous example, Oreos/drugs = lots of dopamine release. Much of this dopamine activity occurs in an area of the brain called the Striatum.

Another group of researchers gave people an fMRI scan (functional magnetic resonance imagingthis is a way of measuring which areas of the brain are most active, based on the level of oxygen-rich blood being delivered to those areas) while they were given either an ice-cream based milkshake, or an ever-so-appetising ‘tasteless wash’ to drink. Having a delicious creamy milkshake fed to you through a tube whilst lying in a big magnetic cylinder was apparently rewarding, and there was increased activation of the striatum in the people that drank the milkshake.

*However* The extent of the activation was lower in people that regularly ate ice cream, meaning that their experience of drinking a milkshake felt much less rewarding and just not as good. The implication is that repeated eating of a particular type of food will reduce the Dopamine response in your Striatum, possibly leading to overeating of that foodstuff to try and get the same great feeling as the first time it touched your tongue.

So I must hold back on the cake, or I just won’t appreciate it as much.

 

  1. Cavemen are responsible for ruining your diet

That’s enough about reward, we know eating delicious cake makes us happy, that’s why it’s described as delicious! I’ve never heard the phrases ‘delicious rice cake’ or ‘delicious tasteless wash.’

So how about cake and attention?

It has previously been shown that when people are hungry, they are more likely to pay attention to food-related words, and to recall more food-related items in a memory test. A study in 2010 used a test called the ‘Emotional Blink of Attention (EBA).’ This is based on a test where people are told to look out for a particular image (or ‘Target’), such as a landscape scene, while they are shown several different images in quick succession. However, if another image that is likely to provoke an emotional response is shown immediately before the target image they are looking out for, then they will pay more attention to the emotional image and will be less likely to notice the target that is shown immediately after. Images causing EBA have typically been related to violence, gore or sex.

Cake cartoon1

When people were hungry, the EBA effect was seen when a picture of cake was shown immediately before the target image. This was even the case when people were offered a monetary reward to ignore the pictures of food. They just couldn’t help paying attention to the cake!

Being able to automatically pay attention to food-related things when hungry is likely to be something that helped our ancestors adapt to their environment and be successful at hunting and staying alive. Now, however, food-related things are everywhere, but this survival response remains. That has big consequences for dieters who are frequently hungry – being hungry means you are more likely to notice that vending machine, the café over there and the charity cake sale a couple of floors up at work. Couple this with an urge for a tasty Dopamine response and now it makes sense why sticking to a diet can be so tough!

So basically – cake is like a drug that we just can’t ignore. So why fight it? Have a slice – just not too often!

 

The Biocheminist

 

Imposter!!

For a huge portion of my PhD I felt like an imposter. One day, someone was going to figure out that they made a huge mistake – that I shouldn’t have been put on the course and I was going to get thrown out any day soon. That despite no one showing any concerns, I clearly I wasn’t up to the job.

These thoughts and feelings have a name – it is called ‘Imposter Syndrome.’ It’s apparently widespread throughout academia (although no one talks about it) as well as in other professions and it is more commonly reported in women.

A few months ago – when no longer entirely in the throes of imposter-style thinking, I was called out on it. Imposter syndrome came up in a conversation, and my supervisor looked at me and casually said ‘oh yeah, you have that’ and then the conversation carried on.

Oh no! My secret! It was known all along!

When I decided to write this post, I naively thought that surely, there wouldn’t be much written about this affliction – but I was wrong! The internet is full of posts detailing imposter syndrome within and outside of academia, and the reasons why it may be more common in women.

So instead I thought I’d write about how, on reflection, I believe I came to feel like I was an imposter (and how I’m getting over it) in the hope another early-career researcher will read it, realise they aren’t the only one feeling that way, and can build up their own confidence and move on. And if that encourages someone to stick with research when they feel like they should quit, then hurrah!

 

  1. You don’t know what you know

My undergraduate degree was in Psychology – while it contained some modules on basic neuroscience, it was a world away from the biochemistry/cell biology PhD that I went on to do. For much of my first year I was coasting on barely remembered snippets of A-level biology – I was lacking the absolute fundamental basic knowledge and I had to catch up quick. I also tended to keep the fact that I did psychology quiet, as many ‘proper’ biochemists still see it as a bit of a joke subject with no scientific merit. This did little to aid my confidence and to convince me that I should be there!

When I started my PhD, my supervisor told me something that has stuck in my head, and I have retold it numerous times to other students when they needed some reassurance. It is that:

One of the most difficult things about doing your PhD is learning the difference between what YOU don’t know, and what NO ONE knows.

It is incredibly accurate and describes the stages of my PhD pretty well – in the first year I didn’t know anything (see above!), but I thought that everyone else knew everything. It felt like everyone else was privy to all this information that I just didn’t have, and that made me feel a little excluded, that I was tagging on and just ‘faking it’ to be a part of the group like everyone else.  But, the learning curve was steep and by the second year I was now aware of what NO ONE knows – in both my office and in the scientific community. The difference between ‘them’ and ‘me’ got smaller, and accordingly so did the feeling of being an imposter. By the third year, I knew how to do things no one else in the office knew, and from doing my research I now knew things that no one else in the world knew. And that is pretty freakin’ sweet.

 Kat Kartoon2

  1. You don’t get graded and you get less feedback

I’m a nerd. Always have been. I have always tried to get the best grade that I can – I shot for the ‘10/10s’, ‘A’s, the ‘A*’s and the ‘first class’ – and more often than not, I got them. Academia is somewhat different. And it took me a while to get used to.

There are no grades, and typically there isn’t a great deal of positive feedback either – every experiment doesn’t get marked, each report doesn’t get a score. This was a huge adjustment for me. Coming into my PhD, I was used to having constant feedback on my work – constant reports, coursework, essays and exams were all regularly graded and given back so that I  knew if I was on the right track or not. Without regular reports and grades, I had no idea if what I was doing was correct or good enough – and as I tend to veer towards a pessimistic personality, I could easily convince myself that I was doing everything wrong and didn’t deserve to be there.

The feedback that you do receive in academia can actually be overwhelmingly negative – this is because in order to ensure the highest quality work is being done, anyone reviewing that work has to be highly critical, meaning they are more likely to pick out your errors and mistakes or tell you that your theory is wrong than say ‘wow this is great – A!’ If that reviewer is in a bad mood (or just a mean person that relishes creating student misery), then you also can’t guarantee that the feedback will even necessarily be constructive.

This combination of the removal of active positive feedback and the more frequent occurrence of negative feedback is perfect for breeding insecurity, and consequently feelings of being an imposter. Now, I’m not saying that PhD students should be coddled and told how great they are – the point is to push them and train them up to be confident, independent researchers that can stand their ground and produce the highest quality work possible, so constant hand-holding and reassurance would be damaging. But a little warning that things were gonna be different would have helped!

I’ve probably found this contribution to Imposter Syndrome one of the hardest to tackle – time and experience have proven to be the best solutions. With the more work that I do and the more successful experiments that I’ve run, I have become much better at self-reassurance (although there is the occasional wobble). I have also come to the conclusion that if no one is saying anything to you about what you’re doing, then it’s probably alright – a big deal will only be made about it if you’re doing something wrong! So carry on in the knowledge that you’re doing just fine!

 

  1. The Academia bubble

I am the only member of my family to have completed an undergraduate degree, so doing a PhD has been a pretty big deal. My friends also seem rather impressed by this accomplishment. And getting a PhD IS a big deal! It’s hard! Not a lot of people do it!

All of this is forgotten upon entering the academia bubble.

Kat Kartoon bubble

 

In this bubble, everyone has a PhD. It’s a totally normal thing. In fact it’s an essential requirement for an academic career.  You are no longer the top of your class, no longer the best of a bunch of interviewees – you are bottom of the food chain! Bottom rung of the ladder! In these circumstances, it’s easy to forget that getting a place on a PhD course is an excellent accomplishment, never mind completing the darn thing! In this environment, a new, insecure researcher can lose sight of their ability, talent and worth, while trying to do their best in the shadow of the post-docs, fellows and professors above them.

The solution to this issue? Get out of the bubble and into the real world whenever possible! I particularly enjoy giving my title as ‘Dr’ whenever I’m asked whether I’m a ‘Miss or Mrs?’ As well as being quite entertaining, it’s a nice little boost to the ego. And that confidence is essential to be an independent researcher and keep on going in the face of failed experiments and harsh criticism.

 

  1. My brain

Finally, I believe that one of the biggest contributing factors to my feeling like an imposter is not the fault of the system around me, how people have treated me or even necessarily in reality or logic. It’s rooted in how I think and interpret things. As I have already mentioned, I can typically be pretty pessimistic and negative – this shapes how I’ve dealt with all the points I’ve described above. When I first started in science, I would interpret any criticism (or even lack of!) as an indication of failure and proof that I wasn’t up to scratch. A more optimistic or naturally confident person perhaps wouldn’t struggle with the removal of feedback, wouldn’t be phased by bubbles and would worry less about comparing themselves with other people in the lab (those students DO exist and I find them creepy!).

While my pessimism and negativity hasn’t generally been helpful, the belief that I wasn’t good enough has pushed me forwards to be better. I discovered a ‘screw you – watch this!’ attitude when I came up against individuals who didn’t respect my work. People started to come to me for help and advice.

And eventually I realised that actually, I am good. I am really very good at what I do (and with my British sensibilities that’s a difficult statement for me to post on the internet!).

My negativity and the pressure I put on myself to do and be the best can still sometimes damage the occasional evening (and endlessly annoy my poor husband), but it no longer dictates how I feel about working in research or whether I deserve to be there.

There’s no magic solution for getting rid of Imposter Syndrome – I found that time, experience and allowing myself to indulge in some positive thinking, ‘letting the haters hate’ and working hard pulled me out of it. Recently I was speaking to a colleague in the lab who was recently given a new contract, and she told me she was waiting for them to realise they had made a mistake – so it wasn’t just me! Knowing that countless other people have experienced the same thing gives it much less power, and makes it a much less individual and personal experience.

 

Below are some links to other sites discussing Imposter Syndrome in more detail and how to deal with it:

https://counseling.caltech.edu/general/InfoandResources/Impostor

http://www.apa.org/gradpsych/2013/11/fraud.aspx

http://shriverreport.org/10-ways-to-overcome-impostor-syndrome-joyce-roche/

http://www.huffingtonpost.com/caroline-dowdhiggins/impostor-syndrome_b_1651762.html

 

The Biocheminist

10 Tips For Writing Your Thesis*

*or any other preposterously long document

It’s almost been exactly one year since I had my viva (thesis defence) and earned my doctorate. Three years of hard work needed to be condensed, made sense of, and weaved into some kind of coherent dialogue to be presented to – and sometimes torn apart by – senior researchers and professors.

Writing a thesis isn’t easy. In the UK, there is no minimum word count but the maximum tends to be around 80,000 words – which gives an idea of the size that these things can get to (although typically the average word count for a scientific thesis is about half of that). So it’s no easy feat. But, it can be done! And it can be done without too much stress, too many tears or total social isolation.

For this post, I have decided to share my top 10 tips for writing a thesis, which have come directly from my experience of ‘writing up’ last summer – including both my successes and the power of hindsight following my failures. I hope you find them helpful!

  1. DON’T PANIC!!!

When you first start your PhD, the idea of writing a thesis may be utterly terrifying and completely alien to you. There will likely be a whole stack of them around the lab from students-past filled with nonsensical scientific language, endless experiments, graphs and figures. And all those references!!

‘How the hell will I ever write one of those?’ A book! A whole freakin’ book!?!’

Before you panic or pretend that it isn’t happening until a few months before your submission deadline, remind yourself – it isn’t that bad. First of all, yes it’s an entire book. But, the requirements for submission usually ask for at least size 12 typeface, double spacing, one sided printing and massive margins to allow for neat binding and easy reading. So all of a sudden one page of typed text actually becomes three. Now imagine all those massive books only one third of their size, and it all becomes a bit more manageable.

I also mentioned the word count – but don’t worry about it. It shouldn’t be a concern. Unlike pizza and doughnuts, bigger does not mean better. My behemoth of a thesis was 73,500 words and was BIG. Much bigger than those submitted by my peers, and it came under waves of criticism before even being opened and read. As it was, my examiners agreed its size was justified *phew*, however no one is going to be impressed just because you’ve written more. They will just be annoyed that they have to read it and carry it around. It’s also likely that in a massive thesis, the writing hasn’t been done concisely – therefore making it particularly unenjoyable to read and detracting from all your marvellous work.

bigbetter

  1. START EARLY

It’s easy to think in your first year that a 3-4 year deadline is far enough away to ignore for a couple of years. And actually yeah, it is. A thesis can be written in a few months if given your solid attention. But I don’t recommend it, and when you can lay the groundwork with relatively little effort early on, why not reduce the load (and stress and panic) later?  Try to get in to the habit of making a final figure or graph or image whenever you finish any individual experiment, and collate these figures into a single, easy to find document. I found when writing up, what took up most of my time was fishing out the old data I knew I had somewhere, then making it look respectable and presentable rather than being a half-arsed unlabelled multi-coloured graph lounging at the bottom of a spreadsheet. It’s also easy to get started early on your methods section – whenever you do a new experiment or use a new technique, just type all the details out including where all your equipment and reagents were from. It takes practically no brain power and will save you digging through multiple lab books and a frenzied dash around the lab finding out where you purchased everything. If you can keep up to date with doing these things, then you will save so much time when you come to actually write up your work.

  1. WRITE YOUR RESULTS FIRST

Your results are the easy bit, and a huge bulk of your thesis. I recommend writing them first because – like the methods – they take less brain power or effort to write. Of course you need to put some thought into how you are going to present and order your results, but the actual paragraphs are just describing what you did and then what happened – the more-difficult-to-write reasons why you did it and what it means are reserved for the introduction and discussion sections. If you have an empty page and just need to get something started but your mind is blank or overwhelmed – start with the results. Formally writing out everything you’ve done might also give you a fresh perspective on your work and help you form a good discussion section. Once you’ve got something on the page, it’s much easier to do the rest.

  1. BREAK IT DOWN

This is a particularly useful thing to do for the text-heavy introduction and discussion chapters, but is also beneficial for planning out every single part of your thesis. I mean this as a way of breaking down large sections of text into smaller, more manageable chunks. For example, the introduction chapter can be the most daunting – this is where you need to summarise an entire field of research relevant to your PhD project and introduce the important themes. This was the last section that I wrote and I put it off for a long time. However, by planning in advance what I wanted to write about in each section, I could ignore the chapter as a whole and concentrate on a section of a few hundred words at a time. This doesn’t seem so bad! I completed a lot of writing without really noticing this way, then I could go back and link or re-order the sections as necessary.

  1. WORK WHERE YOU ARE COMFORTABLE

Everyone will prefer to write in different places – don’t let this influence where you do your writing. Many of my colleagues preferred to write in the office because that is their working environment and it put them in the right mind-set. Others prefer the silence that a library can provide. Personally, I found the office too loud and the library too quiet, and instead preferred to slump somewhere at home in elasticated trousers with CSI quietly on in the background. But that’s just what works for me. If other students are putting in 12 hour days in the office or pulling all-nighters at the library (madness!), don’t feel you have to do the same to ‘prove’ that you are working just as hard if that isn’t what works best for you. Equally, if everyone else is working from home but you need the office environment to concentrate, then don’t feel like a loser for going in to write.

 IMG_1049

  1. TAKE REGULAR BREAKS AND MAKE A TIMETABLE

I’m a sucker for a good plan. From GCSE exams up to revision for undergraduate final year exams and for writing my thesis, I have planned when I’m going to do which bits of work. This has several advantages. First of all, like many of my previous suggestions, it breaks the work down into more manageable chunks. For example, if you have planned out your paragraphs and sections, you can then put them into a timetable to plan when you will write which ones – maybe you will have time to tackle 5 sections a day over several weeks, or if you’ve left it late then maybe it will be 15 sections a day in a lot less time! Whatever the case, it gives you a goal to work towards. Another advantage of doing this is if planned well, you can avoid working those ridiculously long hours and all-nighters that we all hear horror stories about. And if free time is expected and planned, then you won’t feel guilty for not working! Bonus number 3! You can even extend this timetable to incorporate which hours of the day you work best – there’s no point strictly telling yourself you will work 9-5 if you never really get going until 11am. So have a lie in! Work from 11-7! Make better use of the hours where you work most efficiently. Advantage no.4 – making this timetable is an excellent little bit of procrastination before you really get going with writing.

Taking regular breaks is also important – you can treat them as little rewards for each section you complete, or as an opportunity to move around a bit or think about something else for a while. This will stop the work becoming too monotonous or tiring, and will actually mean you can concentrate better while you are writing. The length of working time between breaks and the length of break is up to you, but be sensible! If I was writing a section I found particularly difficult or boring, I would take a 5 minute break for roughly every 15 minutes of work – just by checking Facebook or something. If I was on a roll I just kept going until that roll unwound, then I would reward myself with some kind of cake. Or if I did really well, maybe I’d go change out of my pyjamas into proper clothes.

  1. NEVER UNDERESTIMATE FORMATTING & EDITING TIME

This, and my tip about starting early, are both born from wonderful hindsight. Formatting was the only thing that led me into the nightmarish realms of 3am thesis writing. Make your figures to the correct scale in the first instance – I wasted days re-jigging figures I made to the wrong scale that wouldn’t fit sensibly on an A4 page! But even if you do this right, fiddling about with the best placement of figures and text will take longer than you anticipate.

Check your university guidelines on thesis presentation before you start writing. You will need to consider the numbering of headings and subheadings, the preferred reference format (both in text and in the bibliography), page numbering, indexing, appendices… the list goes on. While it’s tempting to do all the writing then deal with these things at the end, on a document as large as a thesis, that can cost you a lot of time and sleep. Set those things up first, then be super smug when someone only bothers to read the guidelines the day before submission.

 

  1. USE A REFERENCE MANAGER

People still write without using a reference manager, and to me that seems insane. A reference manager stores the records of the manuscripts, papers and book chapters that you read, and works with word processors so that you can ‘insert’ the reference you need into your text, then it will automatically generate a bibliography from the inserted references. This means you don’t need to manually go through and check your references, then type them all out then re-order or re-number them whenever you make any edits. You really should use one. There are several different ones out there, and they tend to be free or have free versions. A reference manager will also give you the option of different formats to present your references in – it’s advisable you choose the one that matches with your university guidelines from the start because, although automated, trying to change the format of several hundred references in a few-tens-of-thousands of words document may put your computer out of action for a while.

  1. GET FRESH EYES

Either your own or someone else’s! After looking at the same bit of writing over and over again, you won’t see your mistakes. You will know what you mean and what you wanted to say, so your brain will ignore any spelling mistakes or grammatical errors. The only way to get around this is to do something else for a while then come back to it. When I say a while, I mean at least a day! Write something, do some edits on it, then leave it and work on another section. When you come back to reading the original section, it should be a bit less familiar and any mistakes a bit more obvious. Of course what’s even better is if you can get someone else to read it for you! It is particularly useful if you can get someone who doesn’t work on the same thing as you to read it – someone working on the same thing as you will have similar knowledge and make the same assumptions, so may not notice any errors because they ‘know what you mean.’ Someone unfamiliar will notice the bits that don’t make sense or that you haven’t fully explained. Bear in mind, it takes either great friendship or great coercion to get someone unrelated to your project to read any of your thesis.

  1. DON’T PANIC!!

A reiteration of my first point! But I am now referring to the end of the writing process rather than the beginning of a PhD. You will have made mistakes and there will be errors. While a thesis full of spelling mistakes and sloppy writing gives a bad impression, the occasional misspelt word is no cause for concern – so don’t worry if you spot a few after submission. The examiners know you’re human, and it’s entirely possible (and probable) they won’t notice many of these small mistakes anyway – and if they do they are just ‘minor corrections.’ I missed out my entire index of figures in my submitted version, but it’s not a sticking point in a viva!  Stay relaxed while you’re writing, have a plan, and it’ll be fine. In the New Year, I’ll post some tips on how to survive the dreaded viva itself…!

IMG_1052

 Did you find any of these suggestions useful? Have you got any tips for writing a thesis? Let me know in the comments below!

 

The Biocheminist

How to make a Mammoth Crisp(r)

Did you see the autopsy of the incredibly well-preserved woolly mammoth last week??

I particularly enjoyed watching a group of scientists totally nerding out over a 40,000 year old frozen corpse – especially that one guy who was so darned determined to find a nice bit of mammoth poo! *Spoiler alert* – he finds some!

There wasn’t the same enthusiastic jumping-up-and-down excitement that followed the recent meteor landing, but I suppose there was more risk of a terrible mess.

During the programme, they mentioned a technique called ‘CRISPR’ (pronounced as we always aim to have our chips (or ‘fries’ to Americans) … ‘crisper‘) as a way to change or edit elephant DNA to be more similar to woolly mammoth DNA. And it’s not just mammoth cloners that are excited about this technique – the whole of genetic and molecular science is silently and carefully jumping up and down about it.

That’s because it’s pretty cool. It’s exciting because it replaces older technologies that take a lot longer, costs a lot more and are much more complicated. CRISPR can therefore potentially reduce the method of gene editing down from years to months at a fraction of the price. Although the actual practicalities of getting it to work are pretty fiddly, the general protocol is actually relatively straight forward.

mammoth

So what is CRISPR?

CRISPR is not just a spelling mistake, it’s an acronym. It stands for ‘Clustered Regularly Interspaced Short Palindromic Repeats.’ Or put in simpler terms: short repeated sequences of DNA that read the same forwards and backwards, which tend to group together and have similar sized spaces between them. But ‘SRSODTRTSFABWTTGTAHSSSBT’ isn’t so pithy.

CRISPR DNA is found in bacteria and acts as their main form of defence against foreign DNA, such as from a virus. CRISPR RNA (CrRNA) locates and attaches to foreign DNA with a complementary sequence of nucleotides (see Express Yourself! for more on this). Identifying the intruder by CrRNA signals to a special enzyme, called ‘Cas9’ that can then cut (or ‘cleave’) the foreign DNA, leaving it inactive and harmless. This kind of enzyme is known as an endonuclease. The CRISPR/Cas9 system acts similarly to our immune system, in that it can remember previous infections in order to protect against future ones. The DNA sequence of an offending virus is assimilated into the CRISPR DNA so that it may be quickly identified, attacked and neutralised if it ever has the tenacity to attack again!

How is that going to bring back woolly mammoths? And why is it such a big deal?

Well, because molecular geneticists have been able to hijack this system so that it can cleave and edit the bits of DNA that they are interested in. The CRISPR/Cas9 system can be isolated from bacteria, and expressed in other cell types – such as elephant cells, or human brain cells. This means that scientists can fiddle about with different genes, and see how that changes the way cells function.

For example, imagine that a cell is expressing a gene associated with a particular disease. Stopping that gene from working – or ‘silencing’ it, may be an effective therapy or cure for that disease. To do this, scientists engineer a portion of the CRISPR DNA so that it recognises the gene they want to attack – in the same way that CRISPR would recognise previous viruses. This means that crRNA will track down the target gene, signal to Cas9 to cut it and stop it from working. Voila! The gene is silenced.

Or imagine it this way – a sniffer dog has been given the scent of a criminal they need to track down.

 IMG_1606

The scent acts as its guide to find the target, just as the DNA sequence from an interesting gene acts as a guide for the CRISPR system. The dog can then bring the criminal down, and CRISPR cuts the gene.

So how about gene editing rather than silencing? To do this, scientists hijack a different cellularfunction called ‘homologous recombination.’ Homologous recombination means that a piece of DNA that is broken can repair itself with a near-identical fragment of DNA that acts as a template. In order to edit genes, new DNA ‘templates’ are manufactured in the lab with the required edit, which are then added to the cell. That means that once CRISPR/Cas9 cuts the DNA, there will lots of near-identical templates available for cells to use to repair themselves – therefore editing their gene in the process.

If we take this back to the sniffer dog example, the homologous recombination process would be like putting a skin graft on a nasty bite the dog inflicts on the criminal – it’s not exactly the same as the original skin, but it’s close enough for a repair. Perhaps while they’re at it, the police add an electronic ankle tag so they can easily find the ‘edited’ criminal – this can also be done in cells by adding a fluorescent tag to the CRISPR/Cas9 system so it’s easy to see which cells have or haven’t been edited down a microscope.

And that’s how they might genetically engineer a mammoth! Or treat particular diseases! Or prevent inherited genetic conditions! The range of possibilities is vast, but the technology is still very much in its infancy and needs a lot of fiddling with.

However – the quick, easy and reliable editing of the human genome as a method for treating and curing disease is currently molecular genetics’ enthusiastic hunt for a woolly mammoth turd. We just need to keep on digging.

 

The Biocheminist

 

For more details about CRISPR, see:

http://www.molim.uni-erlangen.de/downloads/Teaching/Hauptseminar_Aspekte/Manuskripre_WS12_13/Tag14_Crisp/2010_Horvath_Science_Review.pdf

http://www.nature.com/nbt/journal/v31/n3/full/nbt.2508.html

http://www.annualreviews.org/doi/abs/10.1146/annurev-genet-110410-132430?journalCode=genet

https://www.addgene.org/crispr/reference/history/

https://www.addgene.org/CRISPR/guide/

http://www.scientificamerican.com/article/fact-or-fiction-mammoths-can-be-brought-back-from-extinction/

Growing cells – it’s a culture thing

Growing cells – known as Cell Culture – is a fundamental process carried out in most biochemistry research labs. Having a never-ending supply of cells available is a valuable resource for researchers. It allows us to manipulate cells and investigate the effects of new drugs in a way that would be impossible, expensive and unethical to do in animal models or in people. They also provide a consistent and plentiful source of material to perform lots of experiments in a relatively short period of time.

There are hundreds of different types of cells, referred to as ‘cell lines’, which come from different parts of the body, different species, and are created in different ways.

OLYMPUS DIGITAL CAMERA

Some neuronal cells growing in a dish

Broadly, there are 2 categories of cell line:

  1. Primary

These cells are taken directly from a piece of tissue, and have a finite lifespan. They will not continue to grow and divide, so are used in short-term experiments.

  1. Continuous

Continuous cells have originated from a piece of tissue, but they have been transformed in the lab so that they continue to grow and divide indefinitely. These are often referred to as ‘immortalised’ cells. The most famous and most common cell line is known as HeLa, which originated from a biopsy of an extremely aggressive case of cervical cancer. HeLa cells are a particular oddity as they appear to have transformed themselves without any manipulation in the lab. HeLa cells have a complicated and controversial history relating to medical and research ethics – to find out more about them, I would highly recommend reading ‘The Immortal Life of Henrietta Lacks’ by Rebecca Skloot (don’t worry, it’s not too sciencey!).

So what do you need to grow cells?

All cell lines are different and may have specific needs, but the basics are the same. Cells are grown in a nutrient-rich liquid referred to as ‘media.’ Media helps stabilise cells and provides the essential nutrients required for cells to grow.

In loose terms, growing cells isn’t too dissimilar to growing a human baby – it’s a case of food in and waste out, and some care in between to make sure they don’t get sick. It’s also beneficial to avoid dropping them on the floor. Media therefore commonly contains the following:

IMG_1043

Growing cells just like growing babies….kinda

Glucose: Provides energy to the cells,

Glutamine: An amino acid that acts as an extra energy source

Phenol Red: A pH indicator, which changes colour if the acidity of a solution changes. Cell culture media is commonly a reddish-pink colour because of the phenol red, but if the culture becomes too acidic, perhaps by cell overgrowth, infection or an accumulation of waste, then the media will turn a gross yellowish colour so it is easy to see when something is wrong. Media needs to be removed and replaced regularly, as the cells will use up energy and consequently produce waste, which is toxic to the cells if it builds up.

Antibiotics: To help prevent any unwanted infections.

Serum: The remaining component of blood after clotting and the removal of any remaining blood cells. The most common serum used in cell culture is fetal bovine serum (from cow fetuses), referred to as ‘FBS,’ and is a by-product of slaughterhouses for the meat industry. Serum is essential in cell culture because it provides all of the components normally present in the body that helps cells to grow and survive, such as proteins, carbohydrates, hormones and vitamins.

Sadly, there is no additive to correct researcher clumsiness.

10492069_10152673986479110_7751108416114478575_n

Cell culture in action using media containing phenol red

But it’s still not quite as straightforward as feeding and cleaning!

Cells have to be cultured in special sterile conditions – because the cells are no longer growing in a complicated system made up of hundreds of different cell types and a functional immune system, they have no protection against infection. The addition of antibiotics to the media helps protect against bacterial infection, but they are no substitute for proper sterile technique!

Sterile technique involves using a special cabinet (or hood) that has a particular flow of air. Air is sucked into the cabinet and passed through a filter to get rid of any nasties before reaching the area containing the cells. Used air is extracted from the cabinet and disposed of elsewhere. Everything that enters the hood is sprayed with ethanol, and all of the equipment, such as pipettes and tubes, are always certified as sterile by the manufacturer and are only ever used once to prevent any potential contamination.

Cells must also be grown in special incubators that carefully regulate their environment – the majority of cells will grow best at 37˚C (body temperature – what a coincidence!), with some humidity and 5% carbon dioxide in the air, which helps maintain the correct pH.

What happens once you have a batch of cells happily growing?

They grow some more!

IMG_1044

Happy cells are growing & dividing cells

Continuous cells will carry on dividing and growing – they will run out of space and nutrients, so will eventually poison themselves and starve if left to their own devices. This means that cells need to be regularly ‘split’ (officially called ‘passaging’) – this simply means that the cells in one flask or dish will be split up into several other flasks or dishes to continue to grow with more space and more nutrients. This method means that cells can quickly be bulked up into huge numbers and can then be prepared and used for various experiments.

I’ve spent the majority of my fledgling research career doing cell culture, so I’m bound to be biased, but I think it’s pretty awesome.

 

If you have any questions about cell culture, feel free to ask in the comments section below, and let me know if you have any other biochemistry or neuroscience questions you’d like answered! You can also follow me on Twitter @TheBiocheminist

The Biocheminist

Cat-calling and Mental Health

It would be difficult to find anyone who hasn’t at least heard about, if not watched, the now viral New York street harassment video (if you haven’t seen it, you can watch it here).

It summarises an all too familiar experience that most women have faced at least once in their lives – and I mean MOST – as a staggering 98% of women surveyed in 2008 reported that they had experienced cat-calling and harassment.  The video has caused an intense internet debate; as well as the majority outcry condemning the behaviour of the cat-callers and demands to change this all-too-common occurrence, there have also been more negative responses including the defence of the men involved and violent threats directed towards the subject of the video.

While a lot of the debate has centred on the acceptability and frequency of these behaviours, and how it can best be tackled, less attention has been given to the psychological effects of experiencing cat-calling and sexual harassment, and their impact on mental health.

So I did some digging. 

While there is a wealth of scientific literature investigating the effects of sexual harassment at home or in the workplace on mental health, the investigation of the effects of street harassment or cat-calling (referred to in these studies as ‘stranger harassment’) is a relatively new development. This came as a surprise to me, as there are studies that date as far back as 1978 that found that women felt unsafe in a variety of social contexts, and a Canadian study in 2000 identified that stranger harassment greatly reduced feelings of safety to a larger degree than harassment by known acquaintances. To put more simply, harassment by strangers makes women feel even less safe and more scared than harassment by a known individual at work or at home.

Sexual harassment has been associated with nausea, sleeplessness, anxiety and depression. However, the literature focuses on two main components that may affect mental health:

  1. Stress

Arguably the main risk of stranger harassment to mental health is its effect as a chronic stressor  – a stressor can be any environmental or external event  that causes stress to an individual, which becomes chronic when it is experienced on multiple occasions over time. For example, an individual may receive one cat-call on their walk to work. In isolation, this could be an unpleasant and mildly stressful event, or may not have any bearing on that person’s day. However,  should that experience of a mild stressor occur every day for months or years, then it becomes a chronic source of stress that can negatively impact mental health.

How does stress affect mental health?

One of the most studied outcomes of chronic stress is depression (which is also one of the reported outcomes of harassment). In fact, a popular mouse model of depression is called the ‘Chronic Unexpected Stress’ (CUS) model, which is created by exposing mice to…well…chronic unexpected stress. This includes social stress, (such as overcrowding or isolation) and predatory stress (the scent or presence of a predator). This is such a popular model for depression, because chronic psychological stress effectively and predictively causes anxiety and depression-like behaviours in these mice.

Predatory stress increased inflammation in several brain areas in these mice – inflammation is the body’s response to threat, and in the short term protects cells from harm. However if inflammation is present for a long time, it can start to cause damage. Increased inflammation in the brain has been found in, and may exacerbate Alzheimer’s disease and depression.  Studies in humans have also identified damage to the structure and communication networks of the brain as a result of chronic stress, which can have a negative effect on learning, memory and mood.

So it isn’t really such a leap to imagine that the fear or threat felt following harassment, and the powerlessness over its occurrence could become a chronic stressor. It can also arguably be equated with the ‘predatory stress’ used in mice.  In a study that focused on the workplace, an association between harassment and poor mental health was identified. Specifically, individuals who experienced sexual harassment early on in their careers were more likely to be depressed later in life. This was the case for both men and women.

  1. Objectification

Objectification is a societal issue that reaches beyond just cat-calling, but its role in stranger harassment has been investigated. The theory of self-objectification in the psychological literature says that when a person is sexually harassed by a stranger, they feel objectified. This causes ‘self-surveillance,’ or for them to view themselves as the stranger views them. This is usually as a sexualised object, with their worth determined by how they feel they are viewed by others. In other words, they are ‘self-objectifying themselves. This self-objectification has been found to have multiple negative effects on mental health, and has been associated with increased prevalence of eating disorders, depression and substance abuse.

However science hasn’t always been able to carry out this kind of study without bias and sexism.

Several studies that I have come across appear to lay responsibility of the effects of harassment on mental health and well-being on the women who have been targeted, rather than on the individuals who commit the harassment. After associating harassment and self-objectification with negative mental health and psychological consequences, it has been recommended that women should be educated in better coping strategies so that they become more resilient to the inevitable objectifying experiences as a way to prevent mental health problems. It is this attitude – that cat-calling/street harassment/stranger harassment is a ‘normal’ experience that should just be put up with – which has allowed it to remain a prevalent and distressing problem in society.

Despite cat-calling and street harassment having been identified as an issue for at least the past 14 years, there has been no reduction in the number of women experiencing it, and there has been very little attention given to the serious effects these experiences may have on mental health. The scientific community has not escaped without bias in this area, although it has identified the association between harassment, stress and depression, and recognised that there may be a substantial psychological effect of frequent harassment. As the role of harassment on mental health gains more attention, scientists are beginning to investigate more thoroughly; including the negative effects witnessing sexism has on bystanders  and some investigation into why some men do it.

There is still a long way to go – both scientifically and socially. But with cat-calling and harassment carrying such strong risks to mental health, perhaps they should be considered as a psychological assault.

For more information about cat-calling and harassment, and how it is being tackled, visit:

http://www.stopstreetharassment.org

http://www.ihollaback.org

The Biocheminist

You can’t spell ‘Love’ without ‘Vole’ – The Neurobiology of Love.

Love. A source of great joy and agonising pain (wait, didn’t I also say that about western blots…?). When we talk about love, we talk about the heart – love is heart-warming, losing a love is heart-breaking, you should enter relationships based on your heart, not with your head!

Nope! Sorry! I don’t want to break any hearts with this, but love is ALL in your head.

A lot of studies have been carried out where the brain has been scanned (or imaged) while individuals are looking at particular photos or carrying out activities and tasks – this is called fMRI (functional magnetic resonance imaging). This method can detect areas of the brain that are receiving higher blood flow, and are therefore likely to be more active. Using this method, it has been discovered that the areas of the brain responsible for regulating your temperature overlap with the areas of the brain associated with social warmth, defined in the study as the feeling of being loved and connected to other people (Inagaki & Eisenberger 2013). These areas were the Ventral Striatum and the Middle Insula (see pictures below for an idea of where these are). The association between physical temperature and feelings of love went so far that when people in the study held a warm object, they reported stronger feelings of social warmth, and those that read meaningful and loving messages from friends and family reported the room as feeling warmer.brain3 brain5

Here is a brain – my brain – with rough areas associated with love & reward drawn on. Left image from the side, right image from above.

Why would this be? How is that useful?

The authors suggest that it could be learnt from birth – many behaviours used to soothe a baby and show it love, such as rocking and being held, occur in close proximity to another person and subsequently cause a rise in temperature. We therefore learn that warmth is associated with being loved and cared for. And no one can deny that a warm hug (or Welsh ‘cwtch’) from a loved one feels pretty darn good!

The same brain areas identified in that study have also shown greater activation when people rate themselves as close to their romantic partner, this and was associated with longer relationship length. In fact a lot of brain areas have been linked to feelings of romantic love, and many of these, such the Hippocampus and Nucleus Accumbens (see previous picture!) are part of the reward system in the brain. The reward system is the network in our brains that makes us feel pleasure and happiness (a reward), often in response to a particular event or behaviour. Activation of this system makes us try to repeat the action that led to its activation in the first place, therefore resulting in another reward feeling – if spending time with a particular person activates our reward system, then we strive to see them again.

Dopamine is the signalling molecule that works within this reward system.

Prairie voles (super cute voles from North America) are the most frequently studied animal on the neurobiology of love- this is because they form monogamous relationships. Voles that had more receptors for dopamine (parts of the cell that are able to detect the presence of dopamine, allowing the cells to respond to it) had increased monogamous behaviour. This suggests that increased activity in the brain’s reward system may improve the longevity and fidelity of individuals in a relationship, because being with their partner feels particularly rewarding.

IMG_1041

Oxytocin has the reputation of being The Love Drug.

Oxytocin is a neuropeptide – which means it is a molecule that is used by brain cells to communicate with each other, although oxytocin is also capable of working as a hormone around the body. Oxytocin is well known as being associated with pregnancy and lactation, but its effects are much broader than that! It can also stimulate social behaviour, such as increasing trust and empathy. Looking back to those adorable voles, monogamous animals had more oxytocin receptors in the Frontal Cortex, Nucleus Accumbens and Striatum, which are the same areas that show increased activity in humans when shown a picture of their partner. A release of oxytocin in the brain during mating was essential for the important bonding to a partner in voles.

Enough of voles – in humans, oxytocin is increased by hugs, social support, massages and orgasm.

In fact, when heterosexual male subjects were given oxytocin intranasally (up their nose!), they rated their partner’s face as more attractive than other women’s faces, and showed increased activation of their brain reward systems. The author  stated that oxytocin could ‘improve the reward value’ of the subject’s partners…which is oh so romantic(!) A sniff of oxytocin in females improved their ability to determine the emotion felt by another person when just shown the eye region of their face – this is called the ‘reading the mind in the eyes test,’ or the slightly snappier ‘RMET‘.

IMG_1040

As well as oxytocin, multiple other hormones have been implicated in the neurobiology of love – testosterone, cortisol and dopamine have all been identified as contributing to either the longevity or demise of romantic relationships. Cortisol is a hormone that is associated with responses to stress, and particularly high levels in couples during an argument were associated with increased hostility and relationship breakup, particularly if levels were high in both individuals. High levels of oxytocin, on the other hand, were associated with increased empathy. High levels of testosterone are associated with competitiveness rather than stability and trust – it is much higher in single men than in men in relationships who no longer need to compete with other males for a partner.

You can be ‘Crazy in Love’ – Beyoncé was right!

The early stage of a new relationship is considered to be a separate phase that creates different and unique responses in the brain. There is a dramatic increase in the love drug, oxytocin, which in turn increases the activation of dopamine-related brain areas. When these areas are so strongly activated, large areas of the cortex experience a reduction in activity, which means that we lose our ability for rational judgement – which is an effect many of us may have observed in our friends in a new relationship! The activation of the dopamine reward system may also make us temporarily ‘addicted’ to our new beau, as their ‘reward value’ is through the roof! It is thought that this early and temporary addiction serves the purpose of keeping us around that person for long enough to form a meaningful attachment.

So yes, it might all be in your head and love might make you crazy, but it’s also a real biological phenomenon. And don’t forget to be romantic – let your significant other know that they have a high reward value, then give ‘em a cwtch.

 

The Biocheminist

Biochemistry is just like cooking… but try not to eat it

When I started my PhD, I was told that if you could follow the recipe in a cookbook, you could successfully carry out most experiments (success being measured here by a lack of spilling/breaking/wasting/ruining/blowing up anything, rather than by the experiment actually working AND giving you the result you hoped for).This is because experiments normally follow a specific protocol, which is fundamentally the same as following a recipe. However, the more I’ve worked in a lab, the more I’ve seen the similarities with a kitchen… So here are some of the regular day-to-day kitchen things used commonly in the lab:

Cling film & Tin foil

Both cling film and tin foil are used on a daily basis – although special lab versions are available, normal supermarket brand versions are used a lot. Cling film is used for pretty much the same thing in labs as in the kitchen – to wrap things up for storage, to stop contamination, spillages, and evaporation. Tin foil is used to keep light out of things that may degrade in light – for example, when working with fluorescent tags and antibodies, the experiment will be kept under tin foil to prevent fading of the fluorescent signal.

Fridge freezer

The success of many an experiment is down to proper storage of your samples, and everything needs a different storage temperature. While the lab has fancy freezers set at -80˚C for RNA and long term sample storage, as well as liquid nitrogen dewars for cryopreserving cells at around -200˚C, there are also regular old fridge freezers. Fridges are set to +4˚C and are used for short term storage of DNA, some antibodies and various chemicals and reagents. Freezers are set to -20˚C, and are used to store all kinds of things, including protein samples, DNA and antibodies.

Microwave

There’s not much to say about this one! In the lab the microwave is used to heat up and melt things, although very rarely would those things ever be considered edible.

IMG_1034

Milk

Marvel skimmed milk powder in particular is a laboratory favourite. It is most commonly used to make up a ‘blocking buffer’ for western blots – this is typically 5% milk powder in a saline/detergent solution (see ‘Western What’s??’ and its comments section!)

Milkshake

Milkshake brings all the mice to the yard – I mean – helps mice learn associations. Sweetened or condensed milk and milkshakes are used as rewards in mouse and rat learning experiments. For example, a mouse may learn to press a lever in response to a flashing light because they are given a drop of delicious milkshake when they do what they are supposed to do. The milkshake is positive reinforcement – exactly the same as treating my husband to coffee & cake when he goes shopping with me without complaining. I hear from colleagues that strawberry milkshake is a mouse favourite (and also a husband favourite).

Yeast

Just like the stuff used in bread and beer! Although for lab use, it comes from a more controlled and regulated source than the dried variety from the shops. Yeast is a single-cell organism – and its simplicity has allowed the creation of various models that can be used to study fundamental processes in cells that are required for life, for example how proteins interact with each other and how the cell cycle works. It has been particularly useful because it is so easy to grow and manipulate.

Nail varnish

Not really a kitchen accessory, but I’m sure someone will have painted their nails in a kitchen at some point. Specifically the clear, quick drying variety is preferred! A common way of looking at cells under a microscope is to grow the cells on a circle of glass called a ‘coverslip.’ Then when there are enough cells, the coverslip is placed upside down onto a glass microscope slide, so that the cells lie between the two layers of glass. Clear nail varnish is then painted around the coverslip to seal it onto the microscope slide and to stop the sample from drying out.

I’m sure there must be more household things used regularly in labs – especially with scientific ingenuity and tightened budgets! I like to think I’m pretty good at cooking, and I can follow a protocol pretty darn well! However, most important of all, it’s of utmost importance to make sure there’s always enough milk, both at home and in the lab, as running out in either place can really ruin my day!

The Biocheminist

N.B. Posts will now be appearing fortnightly rather than weekly, for the sake of the posts on here and for the sake of my experiments in the lab!

Express Yourself!

There is a fundamental part of cell biology that I haven’t posted about yet, but I have skimmed over it briefly in previous posts here & here. I must admit, the link to Madonna is tenuous (at best), but I will be writing about one of the many ways we all express ourselves. In contrast to the expression of feelings that Madge sung about in the 80’s, this form of expression is not under your conscious control; the fundamental process described in this post is: Gene Expression!

IMG_1030

Madonna, expressing herself.

What is it?

Gene expression describes the process by which your cells can convert your DNA (deoxyribonucleic  acid) into other molecules or products that have particular jobs/functions within the cell. The most common example of this is the conversion of DNA into proteins, which can then go off and carry out different jobs around the cell. Different cell types (e.g. a heart cell, a blood cell or a neuron) exist because they read different parts of your DNA, and consequently create different proteins that carry out different jobs and functions (see the ‘instruction manual’ metaphor in this previous post!).

So how do your cells convert DNA into proteins?

This is done by a combination of two processes called Transcription and Translation.

But before I get into that, here are the basics of DNA:

DNA is a double stranded molecule. It can be compared to the two sides of a zip (or zipper) that fit together in the middle. Instead of the teeth that fit together on the zip, DNA has individual nucleotides (also called ‘bases’). These are simpler molecules that are the building blocks of DNA. There are four different nucleotides:

Adenine (referred to as A)

Cytosine (referred to as C)

Guanine (referred to as G)

Thymine (referred to as T)

In the DNA ‘zip,’ an A on one strand is always paired up with a T on the other strand, and a C is always paired up with a G. These pairings (perhaps unsurprisingly) make up Base Pairs.

Transcription

The first process that occurs in gene expression is transcription, and happens in the cell nucleus.

This is the way that DNA is converted (or Transcribed!) into RNA. RNA (ribonucleic acid) is the single stranded equivalent of DNA. Like DNA, it is also made up of four different nucleotides; however while it has the A, C and G nucleotides, it has Uracil (U) in the place of T. The two strands of DNA are first separated by an enzyme called DNA helicase, so that the nucleotides are no longer paired and are exposed ready to be transcribed. Another enzyme, RNA polymerase, then starts ‘reading’ the nucleotides along the open strand of DNA and creates a complementary strand of RNA. This piece of RNA is referred to as the transcript.

Not all of your DNA is transcribed all at once – only the genes that are needed for that cell at that time are transcribed, so the single strands of RNA tend to be much shorter than the double strands of DNA. There are actually many different types of RNA that exist within cells, and they can carry out different functions. However, the form of RNA that goes on to help create proteins is called messenger RNA, or ‘mRNA’ for short.

transcription

Translation

Translation is the process where mRNA is converted (or ‘Translated’!) into a protein. After its creation, mRNA moves into the cytoplasm of the cell, so this is where translation occurs. To understand how translation works, you need to know these five things:

  1. 1. Proteins are made up of chains of amino acids.
  2. 2. Different combinations of amino acids make up different proteins
  3. 3. A set of three nucleotides in a row will ‘code’ for an amino acid. This sequence of three nucleotides is called a ‘Codon.’
  4. 4. Different combinations of nucleotides will code for different amino acids
  5. 5. Therefore the sequence of nucleotides on a strand of RNA provide the instructions for a particular chain of amino acids, which in turn create a particular protein. A different sequence of nucleotides on different strands of RNA will therefore provide the instructions for a different chain of RNA, resulting in a different protein.

translation 1

So how does translation occur?

A molecule called a Ribosome attaches to the mRNA – ribosomes are like tiny protein-processing factories, and guide the translation process. The ribosome attaches to the first codon – this guides another form of RNA, tRNA (transfer RNA), to that codon. tRNA forms a link between nucleotides and amino acids. On one side it has a codon, and on the other side it has the amino acid that the codon represents or gives the instruction for.

The tRNA needs to have a complimentary codon sequence to the mRNA; if you remember that nucleotides pair together –an mRNA codon made up of CCG would require the tRNA to have a complimentary codon of GGC in order to pair up. This process makes sure the correct amino acids are assembled in the correct order.

The ribosome moves along the mRNA, recruiting tRNA with its attached amino acids as it goes. The amino acids then form a chain, which creates a protein. Once the ribosome has finished moving along the mRNA, the constructed protein is released, and translation is complete!

translation 2

Transcription and translation are complicated mechanisms, but hopefully I made that clear enough to follow! However, they form a fundamental part of gene expression, which underlies how our bodies (including the best bit – the brain (obviously!) work and grow.

laby

Labyrinth, thinking about gene expression

And although Madonna may have missed the mark, Labyrinth’s more recent version of ‘Express Yourself’ might be little more accurate when he says ‘Being myself is something I do well’ – Yup, thanks to biochemistry and cell biology, we all express ourselves, and generally we do it pretty damn well!

The Biocheminist

%d bloggers like this: