Cottrell Scholar Awards - 2015
Activation of the Innate Immune System with Light: A Chemical Biology Approach to Improving Vaccination
Vaccines are among the most effective human health inventions ever, yet precisely how they work remains unknown.
What is known is that most effective vaccines activate multiple Toll-Like Receptors (TLRs) located on dendritic cells, the tree-like cells (Greek, dendron, tree) found in our lymph nodes as well as other immune system organs such as the spleen, thymus and tonsils.
These receptors seem to interact and cooperate.
However, according to Aaron Esser-Kahn, assistant professor of chemistry at UC Irvine, these synergies are not understood at a cellular level. Esser-Kahn has received Cottrell Scholar funding to investigate vaccines at the molecular level.
“To protect us, our immune system must decide if more than a hundred billion molecular entities are self or not self,” he said. “To do this, single cells must weigh and examine unique chemical signals processed by more than 20 different receptors [TLRs].”
In the process the dendritic cells essentially manufacture new genetic codes in response to a vaccine. To understand how this molecular code functions within a cell, Esser-Kahn is designing “photo-activated agonists” of two specific TLRs known to work well together.
An “agonist” is a chemical that binds to a receptor and activates the receptor to produce a biological response. “Photo-activated” indicates the chemicals are driven by precise wavelengths of light and forced to attach themselves to the TLRs.
After creating these chemicals, Esser-Kahn and his research associates use advanced microscopy and other techniques to study how the two TLRs coordinate at the sub-cellular level to increase the body’s innate immune response.
The knowledge that results from this work may help create the first tools to simulate activation of TLRs as they occur in a biological system.
“Using synthetic chemistry we may then be able to decipher the ‘code’ necessary for chemists to start designing immune responses,” Esser-Kahn said. The end result could be more potent vaccines for many types of disease.
Esser-Kahn will use some of his Cottrell Scholar funding to develop innovative methods for teaching undergraduates about organic chemistry. These methods include a “flipped classroom in which students learn content online by watching video lectures, and homework is done collaboratively in in class. He also hopes to make learning “addictive” by developing various games and guided “challenge sets.”