Protein Ties that Bind

By Stephen Shoemaker, May 23, 2017
National Institute of Health grant to help Ithaca College Professor Te-Wen Lo explore protein-binding and cell function.

The search for purpose is easy—at least on the cellular level.

At that scale, pairs of proteins determine a cell’s function: A receptor protein that juts out from the cell connects to external proteins coded with instructions that dictate how the cell should develop or operate within an organism.

But if something goes wrong with that receptor protein, the cell won’t carry out instructions properly, which can lead to disease, including certain cancers.

Te-Wen Lo, a professor of biology at Ithaca College, is researching the dynamics of a particular protein receptor. Though her work is conducted on miniscule worms, the results can be extrapolated to the genetic equivalent in humans.

“The hope is that by learning more things about how this receptor functions in this tiny little worm, we can better understand the role of the human version in human diseases," she said.

Earlier this year, Lo received a grant from the National Institutes of Health totaling $337,519. The funds from NIH will aid her research into how those receptors—specifically the fibroblast growth factor, or FGF—can cause a cell to operate any number of ways depending on the instruction-bearing protein, or ligand, it binds with.

In complex organisms like humans, there are several locations on the FGF protein that can bind with over 20 different ligands, in any number of combinations.

"You can imagine that matrix of interactions gets very large,” Lo said.

So her research actually focuses on the version of the FGF receptor found in a less complicated organism: the tiny worm Caenorhabditis elegans. She’s examining how different structures within the worm’s EGL-15 receptor protein influence its cellular mechanisms. EGL-15 has one receptor capable of binding with only two ligands.

"So it's a much simpler system, and it's much more easily ‘manipulate-able,’” she said.

Depending on which of the two ligands EGL-15 binds with, its cell will either play a role in fluid regulation in the worm, or a role in reproduction. A better understanding of how the receptor protein works—what turns it on or off, so to speak—could eventually help inform better drug treatment for human diseases in which the FGF family of protein receptors play a role.

The NIH grant money will go toward two research aims designed to understand how EGL-15 turns on and off. In the first, genetic sequences in the EGL-15 strand that play a role in the cell’s two possible functions will be identified from the two sections known to bind with ligands. Then mutated genes will be introduced to determine what specific components are interacting with EGL-15.

The second research aim will isolate mutated versions of the EGL-15 protein in a test tube. Some of those mutations are confirmed to prohibit the reproductive role of the cell. Ground-up worms will be added to the tube to see which proteins in the worms interact with the mutated receptor.

Lo’s work is a collaboration with researchers at Northeastern Illinois University. The grant money will also help fund undergraduate student researchers in her lab this summer, and allow her students to attend conferences.