I’m a new PhD student at the National Institute for Medical Research. I’m fresh out of university having graduated from King’s College London this summer. I’m in the systems biology department and have a research focus on conserved non-coding elements. To me, this makes sense. However to a lot of people they look at me like I’m crazy. Not because I’ve decided to do a PhD in research science and that in itself may result in some form of psychological breakdown but because, once I’ve explained a bit more about what exactly CNEs are, they realise I’m ‘just looking in the gaps between genes’.
It’s one of the easiest ways to explain what regulatory elements are, bits in the gaps. But that doesn’t mean they’re any less important than the bits either side of the gap – the genes themselves. Someone tried telling me that statistically I would never find anything or the chances of me finding anything were so low that I wouldn’t have any results by the time I’m 30, let alone in the 4 years I have to complete my PhD, because “pretty much all the disease mutations we’ve found so far have been in the genes”. Aside from the fact I realised I’d only be 3 years away from being 30 by the time I finish my PhD (and subsequently scared myself rigid into making a life plan including a tight schedule for engagement, marriage and children) I also replied with what I find a glaringly obvious answer: that’s because we’ve only looked in the genes so far anyway. Track back to before we developed sequencing technologies and most of the diseases we knew were because of poor diet, the environment and cleanliness (or lack thereof) so why bother looking in the genes? Now we’ve moved on, discovered many mendelian and non-mendelian disease causing genes and mutations, hundreds of them. However, by looking at just the coding regions of the genome we are missing out around 98.5% of the DNA sequence in humans. When the human genome was first sequenced, the surprise that its millions of bases only held around 20,000 genes led to the labelling of much of the ‘gaps’ as ‘junk’. Why is it then that some of this ‘junk’ is so highly conserved over millions of years in evolution?
That’s kind of the idea behind everything I’m doing. There’s a set of CNEs that are conserved in vertebrates, so highly so that we can compare those in zebrafish, humans, pufferfish and mice and they’re the same. If a sequence doesn’t change over that sort of evolutionary time and distance surely it is important? We already know that there is more behind the ‘junk’ DNA so surely discrepancies, insertions, deletions and mutations in these regions could have phenotypic effects? Albeit uncovering the extent of these variations’ effects on disorders and anomalies would be trickier than how a single base change in a coding region could cause a genetic disorder as we are yet to uncover the code, grammar and spelling of these non-coding regulatory regions (if only it was as simple as the base triplet into amino acid version seen in coding regions…). The principle thought behind the theory would say that in a region as highly conserved as the ones we’re investigating, a single base pair could make a dramatic difference as it’s not seen in wild type organisms (the same with insertions and deletions). However we need to prove this. We need to decode the non-coding areas. We need to find a disease-causing mutation in these conserved CNEs. We need to prove this through a functional assay. We need a PhD student to sequence cohorts of hundreds of people with developmental disorders and anomalies and then analyse the data to find these, oh wait… When we find these (because we will, others already have and I’m a bright eyed bushy tailed new PhD student who believes I’ll have some form of answer in the next 4 years, let alone by the time I’m 30…) hopefully it will slowly start steering the balance of research from 99% exome sequencing to a more equal balance between exome and regulome searching. Our genes are crucial to who we are, but we can’t just ignore all the ‘gaps’ in between. They’re full of lots of important stuff too!
- Alexander, R. P., Fang, G., Rozowsky, J., Snyder, M. & Gerstein, M. B. Annotating non-coding regions of the genome. Nature reviews. Genetics 11, 559-571, doi:10.1038/nrg2814 (2010).
- Epstein, D. J. Cis-regulatory mutations in human disease. Briefings in functional genomics & proteomics 8, 310-316, doi:10.1093/bfgp/elp021 (2009).
- Nelson, A. C. & Wardle, F. C. Conserved non-coding elements and cis regulation: actions speak louder than words. Development 140, 1385-1395, doi:10.1242/dev.084459 (2013).
- Woolfe, A. et al. CONDOR: a database resource of developmentally associated conserved non-coding elements. BMC Developmental Biology 7, 100, doi:10.1186/1471-213x-7-100 (2007).
- http://scienceblogs.com/evolgen/wp-content/blogs.dir/296/files/2012/04/i-9e2a23088c9980f92d903a97e602c0af-noncoding_dna.jpg from https://www.sciencenews.org//node/21410 (image)
As a student I often open my email inbox in the morning to see a barrage of circulars aimed generally at postgraduate students, PhD students and researchers. Often the former are less relevant than the latter and sometimes within them are invitations to take part in research studies. Recently however I have noticed a developing trend of branching the apparent gap between science and art. However for me there has never been much of a gap in my eyes, I’ve always thought that scientific images and drawings could be beautiful. It has been a geeky aspiration of mine to have my own karyotype printed on a canvas and hung somewhere in my house. So the idea that there are art competitions out there dedicated solely to ‘research images’ is brilliant in my eyes. It’s another way of showing the world what we do in an aesthetically appealing manner.
In addition to these university led competitions and galleries (see UCL’s Research Images as Art / Art Images as Research page) I have now been shown a piece performance art and animation that has pushed my ideas of how our scientific methods, research and theories can be presented. I have seen creative animations describing research topics and theories before (check out this video explaining a PhD thesis in 2 minutes run through phdcomics.com/tv/) however today I was shown a trailer for ‘Theory of Flight’ by Anna Lindemann. She is a biology graduate from Yale who has crossed over from a possible career in research to take a master’s degree in electronic arts. Describing herself as being in the ‘hazy territory’ as ‘a “science” person around “art” people, and an “art” person around “science” people’ it seems like she has found just the right balance between the two disciplines. As she not conducting research herself, she looks to describing (incredibly up-to-date) theories of “evo-devo” – evolutionary developmental biology – and biological processes. One thing that stuck out to me was how Anna describes her process as a lot of trial and error. This is very similar to the way researchers get to their answers. You have a general idea of what could work but there’s a lot of tweaking of protocols, branching of ideas and, if it all goes pear shaped, scrap it and start again! Theory of Flight has been shown at many science/art crossover events such as the Experimental Media and Performing Arts Centre, the Entertaining Science series, at “Survival of the Beautiful Wonder Cabinet“, as well as working with high school students through the ArtScience Prize. Just that list shows how Anna has been continuously closing that gap along with many other members of the scientific community.
Cross-disciplinary creations to merge the beauty of science with the beauty of art allow us to reach a wider audience and appreciate what is being discovered every day in the labs. In fact, I believe that a scientist should take a step back from their work at times and view it as art in order to remind themselves that the things they are learning, discovering and contributing to the world are important, incredible and often very naturally beautiful. So with that I will leave you with one of my favourite pieces of art. The Brainbow technique is a method of individually labelling each nerve cell over space and time in different colours. This can be visualised in a developing brain and results in the most incredible images like this…
***additional material found on 21/10/2013: http://nimr.mrc.ac.uk/mill-hill-essays/emerge – a short piece on an installation artwork in my workplace
Livet, Jean. “The brain in color: transgenic” Brainbow” mice for visualizing neuronal circuits].” Médecine sciences: M/S 23.12 (2007): 1173.
Lichtman, Jeff W., Jean Livet, and Joshua R. Sanes. “A technicolour approach to the connectome.” Nature Reviews Neuroscience 9.6 (2008): 417-422.
So I guess I should probably give a brief introduction to me. I am a first year PhD student at the MRC National Institute for Medical Research. I’m a systems biologist having just graduated from King’s College London with a BSc in Molecular Genetics. I count that as the ‘fancy stuff’. In my mind I’m a young female research scientist with a bright future ahead of me. I’m also well aware that a PhD can wear you down so in around a year or two I might not see such a big bright future and more a dwindling hope that one of my experiments may just replicate itself… In the meantime I’ll be blogging here, a bit about what I do (although not too much as every scientist’s work in progress is always a bit hush hush) and a bit about what I read and see in the news. Public and media engagement with the scientific community and researchers is and always will be important. If a researcher can’t explain what they do every day to a random member of the public on the street then either they don’t understand it enough themselves or they do but no one else ever will, and what’s the point in either of those two scenarios? So hopefully everything I put down here will be understandable but if I start getting carried away (which is far too easy, Ive been in enough talks and seminars to know that a time limit is emphasised for a reason) then let me know! I’ll try and answer questions, get involved in debate and fill in any blanks wherever possible. Enjoy.
Research is what I’m doing when I don’t know what I’m doing.
-Wernher Von Braun
(image courtesy of www.phdcomics.com)