Friday, October 30, 2015

Day Four- Inject some energy into the week.

Happy Thursday people of the web-world!

Over here I've had very busy day full of challenges and thankfully some accomplishments to keep my spirits up!  But I'll save the tales for another day- bear with me :)

However in a few hours I hopefully get to see all of the lovely ladies of the TSS lab back home in Oxford as I call in for our technical meeting.  This means a distressingly early start- but I do get to show them the work I've done so far and get their input, most likely while I wear pyjamas and try out something called "pumpkin pie".  If only all meeting could be this way...

Peace and Love,
L

Wednesday, October 28, 2015

Day 3- Mounting the challenge!

Well done on sticking with me- if anyone has! I can live in hope…

Today is an awesome day.  I’m sure I will look back on it and think how menial today’s accomplishments were but for now I’m going to live in the moment.  As I’ve previously discussed I work with fish, but I missed out the part where they GLOW :)  I will get back round to that- I promise, but tonight I’m going to keep it brief.  I think my fish are possibly the most beautiful things on the planet, of course I do they are my molecular biology babies, however even other people think they’re pretty too.  Today I was shown how we are going to use a very powerful microscope to look at how cells that contain my protein move and divide into more cells, in the head of a fish embryo from approximately 12 hours old.  This had many steps to get the perfect picture and although I didn’t get a cover shot, I’m starting to understand the process of how to get one.  
A key task is getting these baby fish to be in the correct position, without mushing them.  At this stage they are about the size of an uncooked piece of couscous (#OverheardInWaitrose) and about the consistency of toothpaste contained within a tiny tissue paper bag- yep pretty mushy.  In the wild these fragile embryos are contained within a protective case called the chorion, which they eventually hatch out of much like a chick out of an egg, we have to remove these chorions so we can closely look at the embryo.  Anyway I’ve been practicing how to put these embryos into a special type of jelly that gently holds them in place, is translucent so we can see the embryos and still allows the embryo to grow- this is called "Mounting".  I still need to polish my embryo-orientation skills, but they are a lot better than they were this morning!  I also practiced getting these embryos out of the jelly and cleaning them off so that they can continue to grow up happily to adult fish, this actually went surprisingly well and they are all still happily swimming in their dish now several hours later.
As with anything that involves a computer, the next task is getting it to play ball, today ours was more in the mood for being a bit stubborn, but my supervisor over here fixed it in the end- hurrah!  Yes- regardless of complexity the computer specialist will always recommend turning it off and then turning it back on again.

As our prize for bearing with it, we now have a 3-dimensional video of the Scl-containing cells moving in the head of the zebrafish as it develops (grows/matures) over a 4 hour period- IT IS FANTASTIC (to me, at least). We can resolve for the first time exactly how these cells are arranged at this early stage and can even follow individual cells as the move around the head of the fish.  Already this has thrown up some interesting questions, that I’m keen to delve into over the coming days.

However students can not live off data alone, so I am off to hunt & gather and get some sleep so I’m ready for what looks to be a good day tomorrow.

On a side note today was actually quite chilly, so some of the clothes I have brought with me might actually be suitable on this trip hurrah!  And by chilly I mean 25 degrees Celsius rather than the 32 degrees we had at the beginning of the week, which is just unnecessary really.  Also on day three of trying to get a bit fitter, let’s see how long I can resist the multitude of temptations that American bakeries have to offer…

Over and out,

L

Tuesday, October 27, 2015

Day 2- Finally fish!

Welcome back! I hope you've had a great day out there and are ready for another peer down the microscope into my adventure. By now you may be wondering why all the fish references- well this is because I study how the protein Scl works in zebrafish. These small freshwater fish have beared with me through the trials and tribulations of my PhD research and are definitely one of my favourite aspects of my project. 

When someone tries to work out how something works there's a lot of tinkering plus trial and error that goes on. My project is aiming to understand how the blood and circulatory system forms in the embryos of vertebrates, so in some way I need to poke around with the inner workings of this complex mechanism, to see how everything fits together. 

Fish are a fantastic choice for this type of research as they offer a balance between ease and relevance/morals. For instance if you're going to investigate how a Ferrari engine works, the most relevant model to work with is a Ferrari, however there aren't that many of them, they're super expensive and some would argue that taking a Ferrari engine to pieces is morally wrong. At the other end of the scale we have the wind-up toy car- this costs practically nothing, they are easily available and no one is going to be upset when they get taken to pieces. However a toy car really is nothing like a Ferrari, yes it has wheels, axles and cogs like the Ferrari but how these are arranged are completely different. 

In this analogy the Ferrari is like a human, if we want to understand our own biological processes and try out disease treatments the most accurate test subject is a human. However some people frown on cutting up babies for research... Ptsh!!  The toy car on the other hand is like a very simple organism such as yeast- these are single celled fungi so more complex than bacteria but still a huge way off humans. We can learn some basic principles from studying them but these may not be conserved (i.e. the same) in more complex organisms such as mammals. 

So back to the fish. Fish are like mopeds (small petrol driven bikes). They look completely different to a Ferrari but actually share a huge number of features such as pistons, brake systems and a petrol driven motor. What we discover in zebrafish is likely to be strongly related to the same process in humans, especially the key components which are crucial for the function of the motor/ survival of the animal. 

A pair of zebrafish can lay hundreds of embryos every week and these reach maturity (i.e. can lay embryos themselves) at roughly three months of age. Another great feature of fish is how the zygote (fertilised egg) is formed: zebrafish are "scatter spawners" so embryos are formed outside the body of the adult and can easily be collected for study without any harm to the adult. In mammals however the embryo grows within the mother so to study these really crucial and early stages the embryos have to be removed from the mother- often harming all those involved.  The embryos also develop on a very pleasant time frame- by 24 hours one cell has divided and differentiated (developed into a variety of tissue types) sufficiently for a functioning heart to start circulating blood, eye and ear have formed and the tiny fish can start to beat its tiny tail (ahh cute!).  A major bonus of fish research is it's much cheaper and easier to maintain 100,000 zebrafish than 100,000 mice, thus research funding can go much further. Finally zebrafish embryos are see-through so we can see all the internal organs developing, blood circulating and the heart contracting without any need to dissect or treat the embryo. Only at 3-4 days post fertilisation so they start to loose their translucent nature. 

All round zebrafish are pretty damn awesome. 

Basically that's why today I am happy that my fish, who have been living out in L.A. for five months, have finally started laying fertile embryos of their own. This means tomorrow I will be able to look at them under the microscope and hopefully get some pictures for you guys. 

'Till then be most excellent to each other, 
L



ps: in no way do I condone testing on human children, even if they are screaming and disgusting germ-ridden little brats.  Their parents are probably more suitable anyway...

Monday, October 26, 2015

Hello interwebs!

Hello All,

Welcome to my blog, this is my first time blogging so bear with me as I recount my tales of scientific endeavour and exploration of the mighty city of Los Angeles!

I'm one very lucky grad student, who with five months left to complete my PhD at the University of Oxford, has come to L.A. to undertake a fantastic 2-month project working with collaborators at the University of Southern California (USC). Back home at Oxford my research has focused on elucidating the role of a crucial protein, called Scl, in the formation of blood and blood vessels as a vertebral embryo grows.  Without Scl mice embryos die of anaemia as the blood doesn't form and blood vessels fail to properly join together to make an ordered circulation system.  This shows how important this protein must be in the complex process of producing a fully functional circulatory system.  Interestingly in humans having too much of Scl in certain immune cells causes them to multiply out of control and leads to T-cell Acute Lymphoblastic Leukaemia , a devastating form of blood cancer.

I have being trying to work out how Scl functions at early stages of the growth of zebrafish embryos, this is within 1 day of the eggs being fertilised.  Scl and the other factors it has so far been shown to interact with, are very similar and seem to act in the same fashion in zebrafish as in humans.  This means that anything we can learn in zebrafish is likely to be relevant to treating human conditions.  Studying how a single fertilised egg develops into a fully formed adult creature, is not only interesting for furthering our understanding of life, but also has potentially huge medical benefits.  If we can work out the necessary steps for a whole organism to arise from a single cell, maybe we can partially reverse it.  Many diseases are linked to ageing, such as cancer, Alzheimer's, COPD and certain organ failures. If we can understand how factors such as Scl are involved in the formation and maintenance of crucial tissues, such as blood vessels, we could potentially use the correct combination of drugs to promote growth or healing of crucial blood vessels.

So over the next few weeks I will try to explain how the research I am undertaking out here in sunny L.A. will help us progress towards a better understanding of how Scl functions in vivo (in living animals).  Hopefully this will be interesting for you and will certainly help me organise my thoughts for writing up my research into a thesis!

Till tomorrow, 
TTFN (Ta-ta-for-now = goodbye)

L