Title "Leveraging disorder in designed biosensor proteins and protein materials"

Dr. Ronald L. Koder, James Peace Chair of Physics

Koder Lab, The City College of New York

Hosted By: Dr. Vincenzo Venditti

The largest destabilizing force in biopolymer folding is the inescapable configurational entropy loss in going from a disordered unfolded state to an ordered folded state. One way that the energy is minimized in evolution is through using the minimum degree of order in the folded state that is necessary for a specific function.  Here I will outline first, our experiments utilizing engineered disorder to create high signal sensing platforms for the detection of chemical- and bio-terror weapons, cancer biomarkers, and cytokines central to cytokine storm in covid and Car-T syndrome; and second, our recent NMR and mechanical analyses of the human protein elastin – the protein material responsible for the elasticity of arterial walls whose entropic elasticity is critical to cardiovascular function. As an extension of this latter project, we have created simplified, highly disordered elastin protein materials that absorb and release high amounts of heat when stretched and relaxed.  These are competitive, in terms energy efficiency, with the best known elastocaloric cooling materials that have yet been observed.  

Bio Sketch

I have led a protein design and synthetic biology lab which has been continuously funded for the past 15 years. As a faculty member in Physics at the City College of New York, the CUNY Advanced Science Research Center and the New York Structural Biology Center my laboratory is uniquely placed to develop new technologies for the research, diagnosis and treatment of human disease. My lab focuses on the design of proteins and enzymes and we developed the supercharging-based biosesning algorithm and the sequence-averaged elastin design algorithm in use by us and others to craft medically useful proteins. NMR analysis of designed protein structure and dynamics is a central aspect of our design algorithm. I am one of the few researchers in the nation with a skillset and a publication record in protein design, enzymology, photonics, solution and solid state nuclear magnetic resonance, synthetic organic and inorganic chemistry. I have a track record of 55 peer-reviewed publications and 5 pending or issued patents and my laboratory has established two active startup companies to bring these technologies to industry practice or clinical trials.

We have developed supercharging-driven ligand induced folding as a mechanism to engender a very large increase in the electric field change upon ligand binding. This greatly increases the signal-to-noise in biosensing, and we are using this to create implantable carbon nanotube-based biosensors for medical purposes and hand-held metamaterial-based biosensors that detect terror weapons for first responders.

In the past five years we have been working on the design and biophysical characterization of natural and artificial elastin proteins both as a way to better understand elastin material assembly and function and as a route toward vascular repair materials.

One major, NIH funded project of ours concerns an artificial oxygen transport protein which we have developed as a model system for both oxygen transport by heme proteins and to study nitric oxide detoxification by heme proteins. Nitric oxide is a key obstacle in the creation of artificial blood substitutes and my work has revealed important underlying thermodynamic and structural features critical to both oxygen transport and nitric oxide detoxification.

Another major thrust is the development of an artificial photosynthetic reaction center both as a model system to study plant photosynthesis and as a ‘biobrick’ used in synthetic biology applications to make organisms photosynthetic.

My graduate thesis work centered on a biophysical and biochemical analysis of a flavoenzyme which reduces nitroaromatics, including explosives. This has gone on to become the central enzyme used to locally activate prodrugs in a form of chemotherapy.