Saturday, December 5, 2015

Hello Interwebs!

I have finally thwarted my own ineptitude and managed to log in to my account- Hurrah!  This is despite google rather unnervingly disagreeing about my mother's maiden name... Do they know something I don't?!

So back on the hamster wheel of science, I was about to explain how my project all kind of fits together by putting it into context with the genome- this is the DNA that makes up the chromosomes of living cells. Rather than a full description of an organism, genomic DNA contains a “how to guide” to building the organism.  This allows each cell to produce the proteins necessary for it to make the jump to the next step of it’s development.  Once it reaches this point it is able to read the DNA which instructs it on the next step yet again.

These “instructor proteins” are called transcription factors. They act as bookmarks binding to particular regions of DNA and marking it to the cell whether to “read” a (generally) neighbouring sequence or not, at a particular time or in response to a particular situation.  For instance, when we get a cut, transcription factor proteins will be made that specifically bind the genome such that the cell is instructed to make further proteins including ones involved with wound healing and immunity.  This allows a small number of transcription factors to bookmark a huge number of target sequences across the genome.

One aspect of my project is to investigate were my transcription factor “bookmarks” the genome, however what I am working on in the US of A is how this bookmarking relates to biological function- ie what do the cells actually end up doing and interacting within the embryo.

A key part of understanding how a collection of cells behave is to see how they interact with other cells that express a different pr overlapping set of transcription factors. For instance by comparing the cells that make bookmarks for brain formation how do they interact with cells that make nerves? Are they originally the same cells? If so when do they separate into different cell types, and can they change back?

Because genomic DNA is a series of instructions on how to make the next step it also instructs cells on how to diverge or differentiate into different cell types.  So as the embryo grows the amount of cells in it increases and the amount of cell TYPES increase too.  This is achieved by using a range of different bookmarks in different combinations.  By attaching fluorescent tags (like microscopic glow sticks!) we can identify which cells are using and making these transcription factors or key proteins.

Currently I’m using this cellular glow stick party to see how different cell types move and change within the embryo.  Initially I looked at how cells that make a fluorescent factor that bookmarks genes required for vessel formation (ie for blood or lymphatics) compares to my protein, which has a different colour glow stick and is thought to bookmark early blood and vessel genes.

What we can see down the microscrope is incredibly beautiful and I could stare at all day.  The majority of a PhD project generally involves working your ass off and having to wait months or years to see any result.  Seeing these embryos forming their blood vessels, heart field and blood cells, is incredibly worth it.

As I progress I hope to look at more combinations of these transcription and signaling factors and see how the cells that make them interact with my cells of interest.  The goal of this is far more than just pretty pictures- this will help us understand the contribution of each factor to the formation of the circulatory system of vertebrates.

Outside of the microscope room, I've just seen Spectre at last.  I'm pretty sure I enjoyed more than I would have done normally back in the UK- just letting the british accents wash over me was a treat!  Also I grew up about half a mile from where they filmed some of this, which gave me lovey warm fuzzy feelings seeing Daniel Craig strutting around my home turf :)  However it did make me realise that being over here may have strengthened my British mannerisms and accent even further, so please don't tease me when I get back and I'm painfully and stereotypically British.  My lab at home teased me very early on for picking up the American pronunciation of "tomato" so I blame them for my rebellious retaliation the opposite way.

Anyhoo, TTFN