Science for Non-Scientists

The most frequent question I get from family, friends and even perfect strangers when they find out that I am scientist is the reply “really? And what do you study?” Normally, this is not a difficult question for me to answer. To one of my colleagues I would say, “I study the receptor tyrosine kinase-like protein, Derailed, which is involved in guidance of the Drosophila embryonic salivary glands.” And this might lead into a lengthy discussion of the role of guidance cues in tissue development and factors that may be downstream of such signals. But to a non-scientist I take a deep breath and try my hardest to reduce my research to the simplest of terms. Something like, “I study organ development in fruit flies.” To which I usually get one of two responses: snickering at the concept of studying flies and/or “so you are trying to grow organs for transplantation?” To which I have now given up on actually answering and just say, “yeah, something like that.”

The truth of the matter is that I know what I am doing is complicated to an outsider- heck it keeps my head spinning most of the time. And it’s not that people don’t get what I’m doing that bothers me; it’s their unwillingness to even try to understand. On multiple occasions I have gone into the long version of my project, and have been met only with glazed eyes and the occasional, “uh-huh.” It’s a rather frustrating thing for me. I love my work and would love to share with people what I do, but it takes a lot of effort and 9 times out of 10 I get cut off mid-explanation with a yawn and “so this is crazy weather we’ve been having, eh?”

But I'm willing to give it another try-this time in writing. So, for you brave souls that would like to know what I work on, in as close to laymans terms as I can, I leave you with my attempt at explaining what it is I’ve spent the last 4 years doing and will probably spend another 2 years trying to tease apart.

First off, Drosophila. The common fruit fly. Not that nasty, black housefly you are constantly trying to kill, but the tiny, somewhat cute little fly that hovers around the aging fruit in your kitchen. This is the organism of my focus and specifically I work on Drosophila embryos. Drosophila lay eggs, which I collect, dissolve off the eggshells with bleach, stain them with dyes that label the salivary glands and view them under the microscope. The embryos are very small (about 500µm) and I easily collect 100's of embryos a day. (If you are really interested in learning more about Drosophila you can check out this website: http://flymove.uni-muenster.de/ . In fact, this site has a whole section on salivary gland development under “organogenesis”).

Salivary glands. My lab studies the development of the Drosophila salivary glands. These glands are similar to our own. They are simple, tubular structures that make and secrete saliva into the mouth of the developing larva (yeah, I know "Kat works on fly spit" ha ha). However, I am interested in the salivary gland while it is forming, well before it is functioning in larval feeding. The salivary glands don’t actually start out as tube, rather they are just a group of cells that are on the surface of the fly embryo, initially no different then any other cells that are cover the outside of the embryo (it’s skin if you will). But these cells receive a signal that tell them that they are not epidermis, but rather that they are meant to be salivary gland cells and need to start forming a tube inside of the embryo. So at the appropriate time in development, they do just that. They move into the embryo and form a tube in doing so. Imagine that you have a ball of dough, and you push your finger into the dough, you form a kind of tube into the ball of dough. Invagination is a similar concept. The cells that are going to form the tube migrate together, pushing their way into the embryo, forming a hollow tube. Once inside the embryo, the glands are not yet in the right place. They have to migrate further into the embryo so that they don't end up in gut or backend of the embryo, but are positionedl near the head, where they are needed to function. I know it is probably hard to imagine this without having a reference, but suffice to say the cells migrate into the embryo and then have to move to the correct location within the embryo before they are positioned to work properly.

Drosophila Embryo


Gradients as Positional Information. Let’s switch gears for a moment and think about how a group of cells may be able to determine where they are located within an embryo. One way is to have a gradient present within the embryo. For example, you might imagine that there is a certain protein that is highly concentrated at one end of the embryo. Those cells close to this source of protein would “see” at lot of this molecule. While those cells further away (thanks to diffusion) would only see a little of this protein. In this way, cells would know where they are in the embryo relative to the amount of protein they are able to detect.

Receptors and Ligands. Don’t let those words scare you. Receptors are the proteins on the cell surface that bind proteins and molecules that are floating outside the embryo. (Like the gradient protein above). Ligands are just those proteins that bind the receptors. Now, I’ve told you that these ligands can provide positional information to cells. But there’s more to it than that. In the case of an active migration, like that of the salivary glands, it is not sufficient for the cells to just know where they are are, they need to know where to go. So they need directional cues as well as positional information. They get this information from those ligands that bind receptors. When a ligand binds, it can send either a repulsive signal (pushing the cells away from the source) or an attractive signal (telling the cell to come this way).

Derailed and Wnt5. So I work on a receptor that binds a protein that is present in a gradient in the embryo. The name of my receptor is Derailed. It got its name because cells that don’t have Derailed frequently migrate in the wrong direction. Wnt5 is the ligand that binds Derailed. Wnt5 is present in a gradient within the Drosophila embryo and provides positional information to the salivary glands. Derailed is present at the very tip of the salivary gland and is able to sense the presence or absence of Wnt5. Wnt5 is located on one side of the embryo, the ventral side. It is responsible for making sure that the salivary glands do not get too close to the ventral side, and thus repels the gland away if it gets too close. It is able to do this because it is present in a gradient, highest at the ventral side, and binds to the Derailed receptor if the glands gets too close, signaling to the gland cells to move away.

Mutants. So how do I know all of this about Derailed and Wnt5? I know because I have mutated the genes that make Derailed and Wnt5 proteins. You can think of a mutation as a mispelling in the DNA keeps a cell from making the protein that gene encodes for. When I look at embryos that lack Derailed and/or Wnt5 (do to a mutation) the salivary glands do not migrate correctly. In fact, they have a very specific defect. The glands curve ventrally. This makes sense because in the Wnt5 mutant, there is no repulsive signal to keep the glands from going too close to the ventral surface. Similarly, in a Derailed mutant, the salivary glands do not have the receptor for Wnt5, thus they can’t sense Wnt5 and totally disregard the fact that they are too close to the ventral surface. Pretty cool, huh?

My model


Future directions. So now that I have that figured out, I get to do all kinds of cool experiments. I can, for example put Wnt5 protein in places its normally not and make the gland migrate away from that new source of Wnt5 (I’ve don’t this experiment and the glands make a sharp turn away from any new expression of Wnt5 protein). One of the major focuses of my research in the next year is to find out how the signal from Wnt5 actually results in a change in direction for the gland. One way of figuring this out, is to figure out what on the inside of the cell is receiving the signal from Wnt5 and Derailed. And how does that signal get propagated into cell movement? These are big questions that I don’t know the answer to. But when I find out I’ll likely start writing up this project for publication and thesis. So wish me luck!!

I know this was a rather ambitious first "real" post on my blog. I hope you will stick with me though. I promise it won’t always be so involved.