Cells like to move it, move it!

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Jigsaw puzzles are one of my favorite hobbies. I love looking at all the pieces and figuring out how they come together to create one cohesive picture. Cell biology, for me, is a little like a puzzle. How do all the pieces fit together? Which pieces connect directly? What happens to the overall image when a piece is missing? The “pieces” are proteins, and together they form the cohesive picture of a healthy, functioning cell.

Cells move? And how?

My love of puzzles and interest in cell biology led me to the lab of Dr. Pascale Charest where we study how cells move. Specifically, we’re interested in chemotaxis, the movement of cells in response to a chemical. The idea of single cells moving might be a little bit weird at first. Your skin stays where it is, thank goodness, and the wave of your hand seems far removed from the movement of individual cells. But still, cell movement is an essential process for most organisms. Bacterial cells rely on chemotaxis to find food, while yeast use chemotaxis to mate. In humans, chemotaxis is important in wound healing and for immune function. It is also one of the things that gets dysregulated in cancer cells, giving them the ability to move to different areas of the body beyond the initial tumor site. 

A forest mold called Dicty

My goal in the Charest Lab is to better understand the molecular mechanism underlying chemotaxis. We study cell movement using the model organism Dictyostelium discoideum, affectionately dubbed Dicty. Dictyostelium is a type of slime mold that spends most of its life as a single celled amoeba. In the wild, it lives on the forest floor and uses chemotaxis to find and feast on bacteria. Under starvation conditions, however, thousands of cells perform chemotaxis towards cyclic AMP, a chemical released by other Dicty cells. This coordinated cell movement eventually culminates in a multicellular fruiting body. 

You can think of a fruiting body like a fluffy dandelion. The stem is full of Dicty cells that will be left behind while the bulb at the top releases spores, like a dandelion releases seeds, that will spread through the forest in search of a better place to live. In the Charest lab, we focus on how Dicty cells perform chemotaxis and aim to understand the role of specific proteins in regulating this process. 

One such protein is called cyclic AMP receptor 1 or cAR1. cAR1 lives on the surface of cells and has both an intracellular section that faces the cell interior, and an extracellular section on the outside of the cell. Its extracellular section detects and binds to cyclic AMP which transmits information to the inside of the cell, eventually leading to movement. I am working to understand the role that cAR1 plays in regulating chemotaxis and the detection of cyclic AMP. 

To revisit my puzzle analogy, cAR1 is a core puzzle piece, and I’m figuring out how it fits in with the rest of the picture that is cell movement. So far, we know that cAR1 is important to chemotaxis but still don’t understand the specific details of how it is important. For example, what other proteins does cAR1 interact with? What happens when cAR1 isn’t present or is mutated? What other proteins are important for chemotaxis, and how do they work together with cAR1? Answering these questions will help us build a more complete picture of how chemotaxis works. 

Specifically, I am interested in how phosphorylation, the addition of phosphate groups to a molecule, impacts cAR1 function. We know that cAR1 gets phosphorylated, but we don’t yet know exactly why phosphorylation is important. To delve into this question, I will mutate cAR1 so that it can’t be phosphorylated and investigate whether cAR1 is still able to function normally and if the Dictyostelium cells can detect and move toward cyclic AMP. Comparing normal cAR1 to the mutant cAR1 will help us identify the role that phosphorylation plays in regulating cAR1 function and chemotaxis. 

Developing a better understanding of chemotaxis using Dictyostelium will provide insight into how human cells move. This will make it possible to develop better treatments to prevent the movement of cancer cells or even help promote immune function. Throughout my PhD I look forward to finding more pieces of the puzzle and working to build a clearer picture of the signaling pathway, protein interactions, and role of phosphorylation in chemotaxis.