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!

Human universe - are we alone?

I have to admit I was really disappointed with the second episode of Brian Cox's latest trip around the world documentary series but I was glad I gave it another chance. I'm a sucker for anything about the possibility of alien life and this 1 hour documentary summed up the possibility for life out there.
Some spoilers to follow.

 In one sense the numbers are stacked in life's favour with there being billions of potential stars and current data suggesting there are billions of planets that could sustain life. Cox does a good job of explaining why the odds vastly reduce when you consider the possibly unique event of the symbiosis that created eukaryotic life on our planet. He then reduces the odds further by introducing the Fermi paradox which states any intelligent life existing 10 million years prior to us would have fully colonised the galaxy. I guess they could be more adherent to the laws of Star Trek in not interfering or civilizations burn out before they can escape their gravity well.

The show ended well with the sobering thought that if we are the only intelligent beings* out there ** then we have a responsibility to protect this unique situation and to go out there and explore. I particularly like the latter idea (it should also help with preserving other life on earth) of us going out there and colonising (preferably empty planets as opposed to conquering others). I'm a firm believer of humanity having to create its own aliens - give us a few millenia on different planets separated by near impossible distances and we'll eventually evolve into our own Klingons and Ewoks.

Anyway - a solid episode that has me willing to give the remaining episodes a chance.

*Don't worry he acknowledges there's plenty of intelligence on our own planet - something I think we really need to acknowledge. His point was that none of these animals are physically capable of building things (with the exception of primates and possibly the octopus with some minor mutations) that would allow them to communicate beyond the stars.

** He sticks to the Milky way for what I assume is the fact that a) all bets are off when you include the universe (as you multiply the chance by at least 100 billion) and b) the distances between galaxies are vast even if you happened to be next door to an intelligent galaxy.

Biology on TV

Bit of a personal slam from a quote on "the Blacklist"

"anyone working with Cullen is doing so in isolation, illegally and for no good purpose"

As an aside, the show is fun but rarely has much biology in it. If anything it has the most glaring example of "why don't you perform a DNA test?" I can think of. It's like the show exists in a world where paternity testing doesn't exist.
Otherwise the biology is usually in the hands of people who could make billions using their amazing findings legitimately but decide to use them for "EEEVILL" instead. Case in point, the episode I quoted from where a biologist who came up with a cure for a disease decided to use it to blackmail people with as opposed to selling said cure. It would have been a dull episode though,
Another curious example of science was in an episode where [mild spoilers for an episode that aired a year ago] a scientist deliberately infects large groups of people with a disease (which he magically turned into a virally bourne version of a genetic disease) in order to find a person with natural immunity whom he could then study and find a cure. I'd like to see the reaction of the review panel looking at that grant outline!

Your life on Earth

I found this cool feature on the BBC today. Plug in your date of birth and height and you'll get a ton of interesting facts from how much a redwood has grown to how far you've travelled through the Galaxy during your life. There's also some interesting/scary statistics regarding population (which ticks up as you read) and use of resources that really made me think - as well as selfishly worry that it's something that could easily be an issue in my lifetime.
Anyway, I won't spoil it all and let you discover the nuggets of information for yourself.

Personality test for Biologists!

Cell Signalling Technology recently came up with a crafty form of targeted social media advertising in the form of "what kind of protein are you?" If my workplace is anything to go by it has prove quite successful.

I got "Chaperone" - "You are a nurturer, your calm and efficient manner brings organization to an otherwise chaotic situation. People look to you for help with projects and advice."

I think many would differ on that description!

I noticed there weren't that many outcomes so I think the following could be included.

p53 - it's all about you, you're the centre of the universe and love all the attention people give you although deep down you know you don't quite live up to it.

Protease - You have a profound effect on everyone you meet - for better or worse. You can release people's true potential or destroy them.

Prion - you hang around in the background feeling like no-one notices you. You'll get the last laugh though as you slowly work you way up to the top, causing others to bend to your will.

Haemoglobin - you are the life of the party, a breath of fresh air. A good motivator of others and able to take a lot of crap off people.

I'm sure there are others feel free to suggest some!

BBC Horizon - Is your brain male or female?

It's one of the classic nature vs nurture questions -  are men and women different due to societal pressures or are there genetic/hormonal factors that allow differences to be observed? The documentary does a good job of presenting evidence from both sides and rather than give us an answer leaves us to judge. The fact the show can't decide whether there's such a thing as a male or female brain renders the title question a bit moot. So you'll be disappointed if you are hoping to get an answer to that. The rest of the show is very interesting though and the parts that stood out for me were;

Showing that monkeys have a gender bias to toys that is the same as in humans. Not sure monkey parents could introduce that bias (although not completely impossible).

Showing that research suggests a correlation between testosterone levels in the womb and the severity of autism. It was also interesting that autism could be seen as extreme "male" behaviour. Women are also exposed to testosterone so can still be autistic but this result also fits the observation that autism is more common in males.

That some of the observed differences in spatial awareness disappear when tested in a way that the subject doesn't see it as a spatial awareness test. This raises two important issues - the tests may have a bias towards a gender and that being told "women can't do X and men can't do Y" can be a self fulfilling prophecy.

That medical treatments may become gender specific. I suspect this one may be skipped over by personalised medicine which is already on the horizon. I guess gender specific medicine could still be a useful stepping stone though.

The one aspect of the show I didn't really enjoy was the male and female presenter format, I can see why there was the temptation to go for that angle but it felt a bit forced having them fall on different sides of the fence. Was that supposed to be a male vs female bias? I also felt one of the presenters was cherry picking the evidence eg refused to accept genetic components for things the other gender is apparently better at but apparently being ok with it when it was their own gender with an advantage. Or maybe that's my gender bias? My sample number of 2 suggests it wasn't.

Usually the answer with these polar explanations is the obvious "a bit of both" and I definitely think that's the case here. With regards to nature we'd be foolish to think the X and Y chromosomes are solely responsible for behaviour, For example if having a Y chromosome is " - 5" for having empathy, there's probably at least "+ 10" for empathy floating around on the other 22  chromosome pairs. this would explain the variety within a gender as well as the fact there are crossovers. Just as personalised medicine will supercede gender-specific medicine, so too will the genome overcome the X and Y chromosomes with regard to behaviour.
In terms of nature; I do think society needs to make a concerted effort to iron out gender stereotypes as the evidence presented in this episode shows how it can make the brain behave accordingly. Far better to convince both genders that they can be ambitious, capable in any discipline and have the full range of emotions than to put either one at a needless disadvantage.

BBC4's "the wonder of Animals"

Chris Packham is back with another science-skewed focus on natural history with his new show "the wonder of animals". Each episode focuses on a species of animal and then looks at the science of how it has become so successful.
The first episode was about Penguins and how their feathers are masters of insulation but can also be used to aid acceleration under water via the release of air bubbles. Another episode claims Foxes can sense magnetic fields for hunting and the science behind bear hibernation is truly fascinating. All of these things have me thinking "how can we use this technology for ourselves?". The muscle-wasting defence in hibernation sounds very useful for incapacitated patients and astronauts. for example.

I think there's still a few episodes left but for those with access to BBC iplayer and like their shows in 30 minute chunks, "the wonder of animals" is well worth a look. Just don't think too much about how this knowledge was obtained - the show neatly avoids that.

Here's a taster