The Martian Trailer

Linking this mainly because of the quote "I am going to science the Sh*t out of this". Definitely need to try and use that one at work today.
I'd probably urge people who haven't read the book to avoid the trailer though as it essentially spells out the entire plot in 3 minutes. I'll get around to doing a review of the book as it has Biology sh*t in it.

Pint of Science 2015!

I'm out of hibernation to let you know that the Pint of Science festival will be upon us all from the 18th May. Combining two of my favourite things - science and beer!
Events are occurring all over the world so have a look to see if there's anything happening in your area.

Last year was a lot of fun so I decided to get involved with the Bristol group again. As you can see, there are a wide-range of topics being covered so there's hopefully something for everyone.
I might be biased but let me draw your attention to some talks I'm involved in this year. I decided to go outside my comfort zone and help with talks not solely focused on biology. Part of the reason for this was that I was jealous of not being able to see  talks that caught my attention last year. Don't get me wrong, it's not that I don't like my own field but I often find the other disciplines more curious - especially for general consumption (I'm not a physicist or material scientist!). So by getting involved in the Planet Earth talks, I knew I'd get to see something different.

On Monday 18th May, we have "Extreme Earth", where we have two experts discussing Volcanoes and Earthquakes. Why does molten rock come out of the earth in the first place? Are we any closer to accurately predicting "big" earthquakes? These are just some of the questions the speakers are hoping to answer. No one likes Mondays. so this is the perfect excuse to brighten the day - along with a great excuse to have a drink.

Tuesday's "Really Wild Show" promises to be an eye-opener on many levels. I have to admit I'm not a fan of wasps but it looks like Dr Seirian Sumner may be able to convince me they are anti-heroes if her tease of "Monarchies, Rebellions and wasps with ideas above their station" is any indication of the presentation itself. Then we have a talk that should put Wally/Waldo to shame as Professor Innes Cuthill discusses animal camouflage, how it works and how we can use it for art and military purposes. I've seen some of these slides and they look excellent - I really can't wait to hear them being discussed in full.

The final night on Wednesday is "climate change" - something we hear about a lot but often with a focus on the politics rather than the science. These talks will discuss the science of global warming and how studying previous climate change (the Earth has never been static with regards to climate) can inform future events and uncertainties.

So if you have time next week, we'd be happy to entertain you and if, for some reason, these talks don't win you over feel free to check out some of the other themes and talks on offer. I can see the benefits of mixing and matching topics too!

Plug over, back to getting everything ready.

Control Freak

A BBC documentary with controls! Always worth highlighting!

The truth about...your medicine cabinet

A one hour documentary looking at the effectiveness of over-the-counter drugs in the UK.
There were several demonstrations looking into the effectiveness of cough medicines (just use honey and lemon) and indigestion treatments (they work but watch what/how you eat) but the control experiment in question was looking at deep heat vs cold creams for muscle injury/recovery. They were actually looking at whether ice vs warm baths help aid muscle recovery (of current interest to me as I have a jogging-related muscle problem)

To do this the presenter had 15 people do the same assault course. 5 of them took a 15 minute hot bath and another 5 took a 15 minute ice-cold bath. Then they followed them over the next few days measuring different factors for assessing muscle pain/recovery. The key thing was that the remaining 5 people didn't take a hot or cold bath after exercise.
The results highlighted the importance of the negative control as hot and cold treatments had virtually the same effect. Those who didn't use either showed significantly poorer recovery. If the negative control had looked the same as the hot/cold treatments we could have concluded neither treatment has an effect but now we know hot/cold treatment is better than nothing!

It's not the perfect experimental set up but I think for a TV show this is the right level and the results hopefully showed casual viewers why the control was important.

The presenter hosted an episode on sugar vs protein diets with his identical twin last year so he clearly likes to get the concept of controls across. Although it seems his twin wasn't taking part in the experiments this time. I guess they decided a higher "n" value was more important than controlling for genetic variance :P


The show itself was surprisingly quite interesting It was somewhat disturbing how many ailments are focused on treating the symptoms when adjusting your diet would prevent them happening in the first place eg diet can solve the need for vitamin supplements and indigestion remedies. It does concern me how we (and I know I'm guilty of it) look for an easy fix rather than a long term beneficial solution. Stubborness, I guess.

Tell me, Flies, tell me, sweet little Flies

I've had this song stuck in my head all day. Simply replace "lies" for "flies" and the song in its entirety is worryingly apt for my research. Give it a go and then I'll give you some context.

I finally managed to delete a gene using CRISPR! So I've been waiting 11 days to see what the homozygous mutants look like.

13 days later (because the food isn't so great) and...

They look absolutely fine.

Bugger. I'll have to wait a few days to see whether they are fertile and a few more until they possibly drop dead or start behaving oddly. Chances are they don't have anything wrong with them which means I'll have to start poking around a little more.

There are several options - a sensible one is to do some genetic interactions with candidate genes (that have a phenotype when mutated) obtained from an interactome I obtained. The caveat there is that it's an interactome for the human protein and not the fly one. Ideally make a mutant phenotype better/worse when adding my mutation to the mix.

Another option is to look a lot closer. Based on expression data there seems to be an enrichment in hemocytes (sort of fly macrophages) and the Central Nervous System. Given I share lab space with experts on hemocyte function and behaviour it seems like it's worth a quick look in that direction. The central nervous system I can delve into with simple things like "is there a difference in size/appearance" but I'd also probably hope to see things go wrong with the flies as they get older.

Anyway, there's a bit of work to be done yet until I find a solid lead. Now I have the mutant I may as well at least establish that it conclusively does nothing before moving on.

So yeah - no, no, no you can't disguise. Tell me Flies.

Biology on the Box

A round up of some Biology shout-outs on TV

Episode 5 of "Fortitude" name-checked PCR several times, as well as making claims like "the DNA never lies". I guess it doesn't if there's no cross-contamination. We also got to see a gilson pipette, which is always a joy. They also claimed that it takes 7 years for every atom in our body to be replaced - although a quick google suggests there's a huge variation in the time it takes for that to happen.
An earlier episode mentioned "Apex" predators too so the writer of the show clearly reads or watches popular science documentaries/journals.

Speaking of documentaries, there was a great repeat of BBC4's "rise of the continents" hosted by Ian Stewart. I missed it the first time around but it was a real gem as each episode was dedicated to a continent (Australia, Africa, Americas and Eurasia) and charted its history. There were loads of things I'd never heard of - such as cratons and Stewart is able to explain things simply without being patronising (although the director unfortunately insisted on having "sherlock"-style thought process/montages). But what does this have to do with biology, I hear you ask? Well, the neat thing about the show is that it linked continental events with evolution such as whales evolving thanks to a shallow sea that once existed in North West Africa. Or how India meeting Asia resulted in the extinction of 50% of the planet's species. There were quite a few others and it highlighted how tightly the environment affects life on the planet - something we'd do well to remember!

The last one doesn't really have anything to do with biology but the partial eclipse in the UK was fun to watch (albeit indirectly thanks to the fear mongering/are people really that stupid of staring at it). It still always strikes me as an incredible co-incidence how on a planet that contains the only known life capable of appreciating it - just happens to have a moon that is the right size/distance from the sun to cause an eclipse. The odds must be minuscule. Maybe the universe just wanted to be appreciated? So, it had nothing to do with biology but it was nice to see people being interested in science indirectly. I suspect most just wanted a selfie or get caught up in the hype but I figure most people will have at least asked what an eclipse was and maybe some of them watched the entertaining "stargazing live" show and learnt quite a bit more. Small steps :)
They had a great segment pointing out that even if astrology worked then it's a month out of date and some people are actually born in the ignored 13th zodiac sign - Ophiucus. I like it when science tries to beat mysticism with its own logic. If you want to check your star sign try it here. Turns out I'm really a Pisces which suits me far better - in fact I'm convinced Astrology is based in fact. Better check what I'm supposed to do for the rest of the weekend.

Science Songs

I have to give a lab meeting tomorrow so quick and easy song it is.

I picked this one because a scientist needs to keep their eyes wide open to spot/connect/interpret potential results. They should also be sceptical and demand to see things with their own eyes every now and then!

With Great Power comes never having to wait for the centriguge/vortex again

The Flash TV show has many flaws when it comes to portraying super-speed (usually the fact that if his speed was always as fast as it is sometimes depicted he'd be unstoppable or the that he can apparently hear faster than the speed of sound) but there's one thing in the intro that rings true if he's a scientist - he uses his super speed to vortex (possibly centrifuge) samples by hand.

It's what I'd be doing. I'd also be using it to sort flies super fast (taking care not to smash them) and better yet homogenise those 24 wrist-destroying Fly DNA samples in a row. Although I guess with super speed the 2 minute spin time would be interminable - although I could always be setting up a massive PCR experiment in that down-time.
Basically if I had that power crime-fighting would have to wait until I had a more secure income than science.

Science Music

I may have used this one before (Every post is exactly the same) but this is another song that comes to mind in a repetitive screen.

Screened 130 of the 450 potential mutant fly lines now. Out of the 6 different deletions I've got one.  As cruel fate would have it, it's in the gene that lies within the intron of my gene of interest. So I potentially have a control mutant for my non-existent mutant of interest. I guess I can't get too pessimistic until I hit the half way mark. As it is the long weekend out of the country will provide a much needed break as there's no way I can nip into work to do "a few DNA prep/PCRS" while away.

Science Music

This song definitely sums up the last couple of weeks at work.

I guess it's the downside of screening. I'm essentially going in the morning and collecting virgin* flies from 350 crosses, crossing these flies to other stocks, having lunch and then repeating the process in the afternoon. Over and Over again.

I guess it serves me right for picking a gene on the X chromosome. This means I have to go for the "maiden" female flies as there's the possibility the mutation may be lethal which isn't so great if you're a male and only have the one X chromosome to play with . It also means that all the males from the crosses are potentially ones where the deletion hasn't occurred so there's no point in using them at all. I was planning on doing some courtesy PCR on the males in the sense that if there is a deletion I'd know it isn't lethal. I haven't really had the time though.  I'll probably wish I made the time if it turns out it is a viable mutation and I could have just picked a bunch of males from each line ONCE rather than twice a day for a week. Let's not think of that though.

Next week, I can at least change the repetition of virgin collecting (not as fun and/or sinister as it sounds) with serial fly squashing (essentially as sinister as it sounds) and PCRs.
I have another mutagenesis screen on the go too but fortunately that one isn't on the X chromosome so it will be an absolute breeze by comparison. Unless it's not.

*Just in case you think I'm some kind of kinky drosophilist I should point out that flies use internal fertilisation to reproduce (like most people do) and not externally by the female dumping a load of eggs and then the male does his manly duties over said laid eggs. For this reason, when doing crosses you need females that haven't mated with their brothers (flies are cool with Game of Thrones plotlines) or you will wind up with progeny you don't really want.
They do it doggy style in answer to your inevitable follow-up question. In terms of "how do you know they are virgins" - you can do it based on time or you can check if they have a black spot on their belly. If they have a spot they are still virgin. It's definitely a talking point at interviews if you put that one on your CV.

Tribyd Theory

I'm getting the science equivalent of nails down a chalk-board every time I hear/read the "three parent babies". Even "three person" winds me up a little bit but at least it isn't quite as emotive. I can see why the media has gone with that option as it is attention-grabbing and sort of works as a summary.

The problem is that I think it conjures up the wrong picture of it being an evenly split contribution from the three individuals and it's bait for conservative types who worry that the "traditional family unit will be destroyed" along with the laziest negative argument ever of "it isn't natural". I'll throw in my "I'm not a mitochondrial geneticist expert" disclaimer but mitochondrial DNA is a separate entity from our genomic DNA (it was probably a different organism billions of years ago), so while the DNA from Sperm and egg are shared 50:50 the mitochondrial DNA always (but not always because - nature isn't as conservative as some want to believe) comes from your mother. By the logic being applied in news headlines this means that the father is always the weaker contributor, genetically speaking. Maybe I'm not giving mitochondria it's due but I don't see them as that much different from the human microbiome (the huge number of micro-organisms that exist in our bodies). They are also largely inherited from your mother (pick them up during birth, from breast feeding and skin contact) but can also maybe pick them up from other people early in life. So you could have lots of "parents".

As for whether the technology should be used, I think a really important thing to remember is that most people aren't going to go for this type of fertility treatment unless they have a strong medical reason for doing so. It's not like Jessica Ennis is donating her mitochondria - although maybe that would make the UK more energetic? I can imagine the worst thing that could happen from this procedure is that it will screw up Mitochondrial lineage studies as the mitochondria may have come from a different person than the genomic mother.

Decoding Annie Parker Review - "BRCA1ng bad"

Decoding Annie Parker is a film about the discovery of the BRCA1 gene and its role in breast cancer.
Here's the trailer.

I was drawn to the film as I thought there may be a good chance of science being represented fairly accurately on film. The problem is that the film isn't really focused on the science. I can understand the reluctance to make a film solely about the science as it's easier to get drama out of a cancer patient and her family (which most people can sadly relate to) than out of research (less people can relate to it). So unfortunately the film is 90% family drama, which is fine if you like that kind of thing but it was all a bit "hallmark" channel for me. The cast is surprisingly good in the sense several of them have broke out since 2013 so there's that.

In terms of the science the thing I approved of most was the fact that it took them a long time to complete the research. It was long even by research standards (16 years). As opposed to the hollywood version which would have been "Annie Parker goes to the Dr in the morning, scientist takes a blood sample, they look at it in 3D under a microscope (or ideally an interactive projection), discover the gene, raise some antibdodies against it in the afternoon, inject her with the antibodies and her cancer is cured by the evening.

They also tried their best to avoid "eureka" moments although there was one scene of Dr King channelling the spirit of Mendel and scrawling on some family trees and suddenly working it all out. I don't know if that event ever happened so I can't be too critical but it seemed dubious.

The other thing I haven't been able to verify but struck me as highly incongruous was that King's research team remained the same for 16 years. That means they either obtained an amazing set of contracts and/or never published anything else and so left to start their own labs. I'm willing to bet this was for dramatic convenience.

I can't really recommend the film as I'm not that interested in such dramas but I guess it does do a good job of highlighting how long research can take and how the knowledge it obtains can provide comfort even when it doesn't immediately provide a solution. It's also a good example of how anecdotal evidence/knowledge can mesh with scientific hypotheses.

Counting your flies before they've eclosed

A bad case of underestimating the amount of work to set up a CRISPR screen in flies.

The last time I tried CRISPR mutagenesis I got 17 adult flies from one injection and 23 from another. 40 single crosses in total and only 50% were fertile. Which meant the 4 batches of PCR screening per founder line wasn't too traumatic (until the point I discovered there weren't any mutants).

This time I decided to increase the number of injections and different mutant designs. I figured 6 injections wouldn't be too much of an extra workload based on previous runs. I mean it would probably result in 6 x 30 crosses so less than 200. Perfectly manageable. Well, I currently have 300 crosses set up and at least another 100 to set up.

If I think that's painful just wait until I reach the stage where I have to collect virgins from 400 separate crosses. Here's hoping some of them are sterile and that there's a mutant in there somewhere!

Even more fun is the fact I have another 2 injections arriving tomorrow.

A little bit of staggering or crosses at different temperatures may be required.

Performance Enhancing Drugs

My department began its trial of free filter-coffee and tea today and it got me thinking of how caffeine is a bedrock of research. I think the drop in publications could be easily measured in an institute where caffeine was banned. It's most obvious use is in keep people awake during those soul-crushing paper revision periods or when you're unfortunate enough to be doing an experiment that takes 12 hours plus to complete. It also comes in handy for spiking alertness during seminars and lab meetings and can lead to discussions/ideas that may never have occurred if you were half asleep. Then there's the social side of a group of scientists talking about their day over a cup of coffee.

Which leads me to the other drug of research - alcohol. Let's not dwell on the negative side of it in science but consider its role in getting scientists to network. I can't count the number of times (possibly due to the amount of drink?) I've chatted with other scientists over a beer and found they are working on something similar or useful to me that I'd be unaware of if I weren't chatting to them at a pub/social event. The other useful thing about the alcohol is that it often encourages some out-of-the-box ideas/collaborations which you both swear you will follow up first thing tomorrow. A lot of the time said ideas may not look so Nobel worthy when sober but occasionally they still do. The key thing here is that as you've got someone else involved your more likely to try those borderline cases which could be inspired (or a waste of time).

Then you have the less obvious drugs.

In terms of drug induced ideas you only have to look back to the 60s and 70s when it seems like any biochemist worth his/her salt was making and taking psychedelic drugs. If anyone ever wants to make a 60s version of breaking bad they could do worse than base it on north American biochemists of the era. It certainly didn't seem to harm Kary Mullis (of PCR fame) in any (scientific) way although it may have been the talking green raccoon alien that helped him? Come to think of it could make a great protagonist for a crazy scientist show set in the 60s/70s. I should get to work on that one.

Another drug that some scientists may not own up to using is cannabis. The obvious use is to help relaxation but I've heard several scientists tell me that it helps them concentrate. Some people just have too many ideas going on in their head at times and a bit of cannabis can help them focus on the task at hand. I guess "smart drugs" could also be used to the same effect and will probably become more common as younger generations who have become almost dependent on them for exams continue to use them at work.

I'm sure there are more drugs that have played a part in research. For the cigarette smoker I'm sure they help in a relaxation way - although it always seems a bit odd seeing researchers smoke outside a cancer research institute (they usually hide them away to avoid bad publicity). It's probably a good thing researchers are researching the effects of drugs on people too. There's probably an incentive to check on possible side-effects.

Science Songs

Had this song stuck in my head. Does it mean I'm being subliminally pessimistic?

Time to Try a Technique!

Happy New Year!

I'll try and get back into the swing of things but things have been pretty hectic in terms of priorities (inside and outside work) and while I was wanting to do an update on some exciting experiments, they've been hitting a few bumps and it's hard to not sound negative about negative results! But I really am finding the current work interesting and, dare I say, fun. For those who are wondering - it's CRISPR in flies. It's looking like it's becoming the "in" technique at the moment, largely because it has the ability to do several things such as gene editing, deleting and tagging with (apparently) high levels of efficiency.
I'm really keen on using it for endogenous tagging but I'm still in the process of evaluating how well it works in deleting genes. So far it's 1 gene out of 4 attempts - hence the negative results. I have another batch coming through next week in a make or break attempt (multiple guide RNA combos). Although I'm strongly considering going down the endogenous tagging route on the off-chance it is more successful.

Anyway, trying something new can actually be a great way to stimulate interest in a project and I'd urge others to leap into these things when given the opportunity to do so. My only caveat is that you have to be convinced of all the cool downstream things you can do with it once you have it working. It may not be CRISPR for you but try and find that up-and-coming (or cool-but-somewhat-scary) technique that catches your attention. I know people who have had fun (and a lot of success) with SILAC and a colleague is currently sinking his teeth into APEX with what's looking very promising (and multi-functional in terms of imaging/labelling). I even heard about a technique today that involves using lasers to "detonate" proteins of interest (Chromophore assisted light inactivation/CALI).

My goal is to hopefully have CRISPR set up in the flies so that I (and others from the lab) can pick a novel gene of interest and;

1) delete it/generate a null
2) tag it endogenously with GFP/HA/Cherry (quicker than generating antibodies in theory)
3) replace gene with point mutations (also under endogenous expression)

Those three things should allow me to do a ton of different experiments - assuming step 1 gives something of interest.

It may not be working perfectly but my new year's resolution (besides negating the xmas spread - also not working perfectly) is to to get it working or find valid reasons to ditch it.

You should pick something too; if you're really up for it, develop a technique from scratch rather than use an existing technique. Imagine how cool it would be to develop the next RNAi or CRISPR? And if you do try to avoid winding up as a van driver - unless that's what you want to do!