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!