A summary of my research for people who aren't experts in biology

Let’s start with the question, “What is life?” Even as biologists, we sometimes struggle with this question. Usually, life is considered to be self-contained and separate from the external environment. As humans we are distinct from our surroundings, protected by our skin. Life should also possess the ability to be different from that environment. Warm-blooded animals, for example, are capable of maintaining a constant body temperature despite the temperature of the environment. In addition, living things can respond to the environment, as plants grow toward the sun and birds migrate south in the winter. Usually, another requirement for being alive is the ability to reproduce; however, even this is controversial. Under this definition, mules are not alive! This rule is usually why viruses are considered to be not alive – they cannot replicate on their own and can only do so upon infection of a host. We often say that in order for something to be alive, it must also be able to die, which means that self-replicating robots from fantasies like Star Trek would not be considered alive (although, could eventual break-down of parts be considered death?) The ability to take in nutrients from the environment and use those nutrients to grow is also considered an aspect of life. Why is it that viruses are considered not alive because they cannot reproduce without a host, when fungi are considered alive despite the fact that they rely on a host (usually a plant) to absorb nutrients from the environment for them? These are just a few of the questions scientists wrestle with in categorizing the organisms around us.

If the definition of life is a bit hazy, things get more complicated as we forge ahead to describe what’s going on at the cellular level. Cells are the “basic unit” of life. Some organisms consist of only a single cell, such as bacteria, yeast, and amoebas. Since a cell is usually no larger than one hundredth of a millimeter in diameter, these organisms are only visible under a microscope. The macroscopic life forms we encounter on a daily basis are all multicellular. Multicellular organisms consist of many cells which have divided up the labor of survival. (An adult human has approximately 100,000 billion cells). In such an organism each cell now specializes in particular tasks. For example, in humans, we have nerve cells that perform sensory functions, muscle cells that allow us to move, skin cells that protect us from the environment, and immune cells that combat disease, to name a few.

It may help to think of an organism as a bakery that produces many types of baked goods and sells them to customers to stay in business. Each worker in the bakery makes one type of baked good: Luanne makes brownies, Heather makes cupcakes, Roy makes muffins, Arnie makes cookies…I could keep going, this is becoming a game to name as many baked goods as I can…but you get the point. Without each worker, the bakery would not be as successful as it is because it would be missing a particular product. The workers rely on each other to all contribute to the well-being of the bakery, ensuring that they continue to have jobs in this rough economy.

Similarly, all the cells in your body are specialized for unique functions, all of which are essential to your survival (and thus your cells’ survival). And, like the workers in the bakery, the cells in your body make things. The most functional type of molecule produced by your cells is the protein. Proteins have many different functions in your body – they can serve as hormones, they form structures (your skin is formed on top of a dense layer of proteins, your hair is composed mainly of proteins), and they perform tasks including digestion of your food, transport of oxygen throughout the body, clotting your blood. Antibodies, which attach to pathogens and help clear your body of infection, are also proteins. Again, this could become a fun game for me. The analogy we come away with is: baked goods are to the bakery as proteins are to your body. People don’t usually line up to buy your proteins from you though…it’s too bad, because your personal bakery is very productive. You end up eating all those baked goods yourself.

How do the workers in the bakery know how to make baked goods? They need a recipe that tells them what to make. The bakery has a big file cabinet of all their recipes (because this bakery is old school and doesn’t know how to store files on a computer). The bakery has to guard this file cabinet carefully and make sure none of the recipes in it get damaged over time so that the workers can continue to make all the baked goods properly. So, the bakery has a policy. When workers are going to make a particular baked good, they must take the recipe from the file cabinet, Xerox it, and put the original back in the file cabinet. They can then take a copy to the kitchen and use that during baking. Sometimes, if a certain type of cookie is in high demand, the worker might make multiple copies of the recipe so that more than one person can make that cookie at a time. Over time, these copies get splattered with batter, burned, dripped on, and otherwise destroyed. These copies can just be thrown away, because the original is safe in the file cabinet.

Likewise, your cells have a “file cabinet of original recipes” for making all the proteins they need to make. This is your DNA. DNA has all the information necessary to make any protein. However, this information is precious. If it were to be damaged, the cell would no longer be able to make the proteins it needs. So, instead of using the DNA to make proteins, the cell uses RNA. RNA is like the Xeroxed copy of the one recipe you need out of the file cabinet. When a cell wants to make a protein, it selects the region of DNA with the information to make that protein, makes an RNA copy of that region of DNA, and uses the RNA as instructions to make the protein. The cell will usually make multiple RNA copies at a time, allowing many proteins to be produced simultaneously. Just like the temporary copies of the baked goods recipes, RNA will degrade over time and new RNA will have to be made.

These are the basic principles of information storage and use in cells. My research is interested in how cells communicate with each other – how does information get sent between cells? One way cells can communicate is through exosomes.

What are exosomes? Again, we are going to have to rely on one of my super-fun analogies. Imagine now that instead of a bakery, your body is the corporate office of a very large company. Again, this is an old school company – they don’t know how to send emails. So, a common way that messages get communicated in between workers is via memos. If a manager needs to communicate something to one of his team, he sends a memo to that person. That person then takes the information in the memo and modifies his behavior accordingly.

Exosomes are like memos for cells. Exosomes are packets of proteins and RNA that can be sent between cells. Because your body has a very active immune system that recognizes free RNA and proteins in your blood as pathogenic, cells have to package the information to protect it from the immune system. This would be equivalent to janitors who come around the office and throw away any memo that is lying around unprotected. Exosomes are basically oily balls that can avoid activating the immune system and safely deliver proteins and RNAs from one cell to another.  This is like having a protective envelope for your memo that tells the janitors not to throw it away.

There are many interesting properties of exosomes. One is that they are tiny. As small as a cell can be (remember 1/100 of a millimeter in diameter), exosomes are 1% to 0.25% the size of cells! This makes it easy for them to travel around the body and slip into small spaces between cells.  Just as different people send different kinds of memos in the office and these memos have a large variety of effects on the people that receive them, exosomes can be produced by many different types of cells and have a wide variety of effects on the cells that take them up. Because exosomes contain RNA and proteins, they can change the behavior of the recipient cell. It’s almost as if one worker at the bakery handed his recipe to another worker and said, stop making what you’re currently making, and make this instead.

We don’t currently know if the information in exosomes is specifically selected by the cell that made the exosome, or if it is a random sample of the RNA and protein made by that cell. Going back to the office analogy, we don’t know if workers are sending specific memos out, or just randomly putting papers from their desk into the memo envelopes with little interest in what happens to them after that. Exosomes may even be “trashcans” for excess material in the cell.  In the office, maybe a worker is just clearing off his desk of old papers that are completely unnecessary to him and sticking them into the memo envelope.

We also don’t know if exosomes are targeted to specific recipient cells. We don’t know if office workers are addressing memos to specific other workers, or jus throwing the memos in to the hallway where other workers are randomly picking them up.

We do know that exosomes are secreted in increased numbers by cancer cells, and doctors are beginning to use exosomes to diagnose and determine the prognosis of certain cancers. This is like a consulting agency being able to come in and read some of the memos that are circulating in the company and deduce whether or not the company is in trouble.

While these are all interesting questions, the drive of my research is to take what we do know about exosomes and make something useful out of it. (I may have joined a biology department but I’m an engineer at heart).  The idea of my research is to see if we can use exosomes to deliver therapeutic information. Again with the office analogy, imagine the business is failing and an outside consulting company can come in and strategically insert a few memos into the office building that will increase efficiency of the workers and help the business become successful. Furthermore, it would be good if the memos could be specifically addressed to people who can have the greatest impact on the health of the company. This is the goal of my research. In order to do this, I have to develop a method for putting specific RNA and proteins into exosomes. I also have to develop a method for targeting exosomes to specific recipient cells. For now, the idea is to target exosomes to immune cells and deliver RNA and protein that instructs those immune cells to fight cancer.