Congratulations to Dr. Gregory A. Hudalla, assistant professor, Dr. Benjamin G. Keselowsky, professor, and their team on their manuscript titled, “Locally Anchoring Enzymes to Tissues via Extracellular Glycan Recognition,” that has been published in Nature Communications. Their collaborative research seeks to address the unmet challenge of installing enzymes within specific tissues to alter local biochemistry while avoiding widespread distribution that leads to off-target changes in organism biochemistry.
 
Despite more than 50 years of active research, the use of enzymes in medicine remains limited by safety issues resulting from unfavorable pharmacokinetics and pharmacodynamics. This is primarily because a small amount of enzyme can quickly convert a very large quantity of substrate into product.

To achieve this objective, they engineer enzymes to bind to extracellular carbohydrates. The key advances with their strategy are: (1) enzyme residence time can be tuned by varying the number of carbohydrate-binding anchoring units; (2) by targeting common carbohydrates, it is applicable to any tissue site that can be accessed via minimally-invasive injection or during surgical procedures; and (3) it leverages conserved carbohydrates, making it translatable across humans and various animal species.
 
The impact of this research is to advance enzymes as therapeutics while also fostering new ideas in protein engineering. The ability to engineer local biochemistry by introducing specific enzymes at the right time and place within the body would afford new opportunities to treat diseases such as cancer, metabolic disorders, and autoimmunity, fight infection, enhance wound healing, and promote tissue regeneration. To realize this potential though, approaches are needed to transiently install enzymes within specific tissues to engineer local biochemistry while avoiding widespread distribution that results in off-target reactions throughout the organism.
 
Nature Communications is a peer-reviewed open access scientific journal published by the Nature Publishing Group. It covers the natural sciences, including physics, chemistry, earth sciences and biology.

For more information see the Behind the Paper story published on the Nature Research Bioengineering Community blog.

Dr. Gregory A. Hudalla, assistant professor & J. Crayton Pruitt Family Term Fellow, was recently awarded a National Institute of Biomedical Imaging and Bioengineering (NIBIB) Trailblazer R21 Award for his grant entitled, “Supramolecular hydrogels for localized delivery of immunomodulatory enzymes.”

The proposed project aims to develop biomaterials with integrated immunomodulatory enzymes as a new treatment modality for inflammatory diseases. States of chronic inflammation resulting from aberrant immune system recognition of self as non-self are a significant clinical and financial burden because they are often incurable, and are typically managed by administering costly biologic drugs that can render patients immunodeficient or immunocompromised. With this award, the proposed research program will develop locally administered biomaterials that can recapitulate natural mechanisms to locally resolve inflammation via enzymes that catalyze the conversion of immunostimulatory signals to immunosuppressive signals.

The Trailblazer R21 Award is an opportunity for new and early stage investigators to pursue research programs of high interest to the NIBIB at the interface of the life sciences with engineering and the physical sciences. A Trailblazer project may be exploratory, developmental, proof of concept, or high risk-high impact, and may be technology design-directed, discovery-driven, or hypothesis-driven.

The NSF Research Advanced by Interdisciplinary Science and Engineering (RAISE) program supports lines of research that promise transformational advances through prospective discoveries that reside at the interfaces of disciplinary boundaries and thus lie outside the scope of a single NSF program. This RAISE project is jointly funded by the Biological and Environmental Interactions of Nanoscale Materials program in CBET Division in the Engineering Directorate, the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences in the Biological Sciences Directorate, and the Office of Integrative Activities. 
 
The multi-institutional team of Dr. Carol Hall, Camille Dreyfus Distinguished Professor at NC State University, Dr. Anant Paravastu, associate professor at Georgia Tech, and Dr. Hudalla, combine their expertise in computational modeling, biophysical characterization, and nuclear magnetic resonance to study peptide assembly into supramolecular (‘beyond the molecule’) structures. This RAISE award supports their on-going efforts to advance understanding of “peptide co-assembly” — the formation of a single supramolecular structure via interactions between two unique peptide molecules — as well as to use co-assembling peptides attached to proteins as a general strategy to create functional supramolecular biomaterials. The goals of this project are to establish a computational-experimental framework to uncover molecular-level design rules necessary to predict peptide co-assembly, and then to use these rules to develop novel enzyme-functionalized supramolecular biomaterials. This approach is anticipated to provide an extraordinary near-term improvement over the current state-of-the-art in enzyme immobilization methods, while also having a broader transformative impact on designing novel functional biomaterials for medical and technological applications.

http://bme.ufl.edu/node/2029