Monday, August 15, 2016

Living double lives

While it is often joked that getting a PhD can be stressful and quite time consuming, for those who choose to utilize field data, it can be doubly so. Graduate students rarely have the time to do much data analysis, or writing, while they collect their data in the field (the same goes for grad students that are teaching). For example: on the hyena project we spend at least six hours a day collecting field data, and then another few hours getting it recorded in legible format, seven days a week. We also have chores to do, and need a bit of sleep and time to relax to be fresh for the next day. So for all of the grad students on this project, this means that they have to double down on their research lives, and plan for time in some form of a lab back home. This could be in a computer lab, where they will develop analytical techniques for understanding audio, video and transcribed behavior, or in a wet lab, where they will be analyzing biological samples like blood, feces or saliva, or in many cases students will use both computer lab and wet lab data. Only then they will finally get to sit down to actually analyze the data, and write it up. While this seems like a tall order, we all still chose these projects through our love of science and discovery. As an example of what this looks like, I will use a current project I am working on alongside a few of my colleagues.

We are interested in a subject called behavioral epigenetics. “What is epigenetics?" you ask, well at the root it means above (epi) genes, in that something above your basic genetic code is having a observable effect on what is physically presented by an organism. You see your genetic code, or DNA, is not the end all of making you what you are (ie your phenotype). A great deal of your physical appearance and behavior, depends on how and when your genes are expressed, and the process of expressing a gene can be modified. What is interesting is that these modifications can be affected by the behavior of individuals around you, and in turn modify how you interact with others.

A possible example
Pene and Ziti [seen to the left with their mom Guci] lost their mom when they were still quite young.
They were still fairly dependent on mom for access to food, defense from other hyenas, and to learn their rank.
Subsequently, these two are somewhat odd compared to most natal males, in that they still have not dispersed,
which usually happens between 2 - 3 years of age, and Ziti [above right] is over five years old now!!!
This variation in behavior may be due to their experiences after loosing their mother,
which could have altered their behavior through epigenetic modifications.
To help explain what I am talking about, I will give a quick explanation of what I mean when I say gene expression. A gene must be transcribed in the cell nucleus, which requires a cluster of proteins called a transcription factor to bind to DNA upstream of the gene that is going to be transcribed. This happens in areas of the DNA called promoter sites. Then the transcription proteins unzip the DNA and make single stranded copies of the gene called RNA. RNA is different than DNA in that it is both single stranded, where DNA is two strands fused together, and during transcription one of the nucleotides that make up the genetic code of DNA (for biology class recall these are “A”, “T”, “C” and “G”) are replaced with a different RNA nucleotide (“T” gets replaced with a “U”). After this the new RNA must be processed, where it basically gets trimmed of regions in the original RNA code that don’t match up with the protein that the RNA was transcribed for. This trimmed mRNA (messenger RNA) must be moved out of the cell nucleus and into the open cell space of cytoplasm, where proteins called ribosomes, along with other specialized pieces of RNA, translate and create the final protein to be used by the body.

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Of course this is a very simplified explanation of gene expression, but it does point out the basic steps, and each of these steps can be varied based on what is going on in and around the organism. Much of this happens very very fast, and variation can be very small with big consequences, making it nearly impossible to study. What my colleagues and I are interested in are permanent to semi-permanent changes to the gene expressions process, that occur during physical development, which is what is commonly termed as epigenetics. One of the most well understood epigenetic changes comes in the form of an alteration in the very initial step of gene expression, when the transcription factors I mentioned first attempt to bind to the DNA upstream of the gene in the promoter region. A simple molecule called a methyl group (a carbon atom connected to three hydrogen atoms) can also bind to nucleotides in these promoter regions, interfering with the transcription factor protein's ability to land and start the transcription process.

Methylation basically interferes with the transcription factor's ability to bind to the promoter,
thereby reducing the efficiency of gene transcription when the gene needs to be transcribed by the body
Here is where things get really interesting. Scientific research has shown that how an organism interacts with its environment while it develops, can affect how many methyl molecules are bound to different promoters for different genes (this is termed methylation). What is really cool, is that it has also been shown that the behavioral environment an individual is raised in, such as variation in maternal care and social interactions with peers, can have large effects of the level of methylation different genes have. In short how you are raised can affect how your genes are expressed as you develop, which can alter your physical appearance and behavior for life!!!

Really cool right?!?! However, in getting back to PhD students leading multiple lives, this means that my colleagues and I must have behavioral data from when hyenas are young, as well as when they are adults, including detailed data about how moms vary their time and care among cubs. We also need to utilize biological samples for us to study RNA levels and DNA methylation, which requires a lot of effort in the lab as the technology utilized to study epigenetic changes is still relatively new, so there is some trial and error work to get done. Finally, we have to develop analytical techniques to combine the behavioral data with the genetic data, while keeping in mind that basic environmental factors, like game availability or rainfall during the year, can have major effects on development and possibly alter epigenetic modifications. 

Needless to say, this is a lot of work before we will even get to the analyses and write up, and nearly all of our colleagues are in the same boat when trying to juggle their field data with their lab data. Granted we chose this, but if you ever see a grad student wandering around aimlessly, or staring off into space, please remember they may be leading double lives.

Special thanks to:
PhD Comics:
Scitable of Nature Education:

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