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.
Tuesday, 17 February 2015
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.
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.
Sunday, 8 February 2015
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.
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.
Tuesday, 3 February 2015
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.
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.
Monday, 26 January 2015
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.
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.
Wednesday, 21 January 2015
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.
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.
Monday, 12 January 2015
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.
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.
Wednesday, 7 January 2015
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