We are interested in how chemicals interact with the innate immune system. We are driven by the idea that we can use chemical tools to design immuno-therapies and vaccines.
The Big Picture: Chemical Approaches to Tackling Innate Immunity
We are inspired by fundamental questions of a chemical nature like: What makes a good vaccine a good vaccine? What is the molecular code the immune system uses to recognize foreign from self? How does this code translate in space and time to let the immune system identify foreign chemical objects? Asking these questions led us to think about designing immune therapies from the bottom up, taking the important elements and connecting them using molecular tools. As chemists, we are intrigued by self-defending chemical systems that protect themselves against a collection of foreign chemicals. We study this problem on two levels: (1) seeking direct understanding of the innate immune system and (2) learning bigger lessons about creating a system that defends itself.
The Nitty Gritty:
Molecularly Coupled Agonist: Bottom up Vaccine Design
The innate immune system recognizes a palate of chemical agonists to “pattern recognition receptors.” What is unclear is how the system makes a decision about foreign versus self. A challenge in the field is combining these chemical signatures together into macromolecular objects to see how patterns work together at the molecular scale. The best vaccines, by their empirical nature, stimulate multiple receptors in a controlled spatio-temporal manner. This stimulation, in our opinion, represents a unique molecular code with no permanent chemical signature to study. We probe these codes using bioconjugation to recreate multi-code, macromolecular signals and determine their influence on the innate immune system. To view our work in this area, please see papers by Rock and Janine in Angewandte Chemie and Chemical Communication.
Photo Activation of Innate Immunity
Deciphering the innate immune code requires probing both space, time, and a series of receptors. This innate immune space is analogous to other chemical spaces. In photo-caging innate immune agonists, we seek to control the spatial and temporal elements of innate immune signaling. To gain the highest resolution, we borrow techniques from physiology, neuroscience, and chemical biology. Perhaps the best activation patterns are not those found in current vaccines. In addition, precise spatial activation of innate immune cells will lead to a greater understanding of how these complex networks interact with each other.
In both these projects, we want to conduct and enable these experiments by making molecules and providing them to the innate immune community to accelerate experiments in this area. If you are interested, visit our collaboration “store” to select different molecular agonist that can be released at distinct wavelengths. If you would like assistance in experimental details please also see the store or the collaboration site for further details.
Chemical Discovery in Innate Immunity
Finally, as chemists, we are intrigued by the full range of chemicals that might stimulate the innate immune system. There are several known agonists, but what of the unknown? We seek to rationally design new molecular entities that stimulate the innate immune system with discrete properties. Analogous to how small molecule synthesis continues to revolutionize pharmaceuticals and the treatment of diseases, we believe the same tools and understanding could be fruitfully applied to stimulating innate immunity.