With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Catherine Leimkuhler Grimes from the University of Delaware to investigate the interactions between bacteria, humans and yeast. Bacteria surround themselves with "jackets" called bacterial cell wall to protect themselves from environmental insults. The ultimate goal of this research is to determine how different organisms bind to and are activated by bacterial cell wall fragments leading to an immune response. This information is critical in understanding how a variety of species have solved the problem of binding bacterial cell wall ligands as an initial step in a stimulated response. Using synthetic chemistry, biochemistry, molecular biology and microbiology, the principal investigator is developing a framework of understanding of how bacterial cell wall ligands are recognized across nature. This work ultimately results in a deeper understanding of how three systems; bacterial, human and fungal, function in a common environment. As part of this CAREER award, the principal investigator is developing creative mechanisms for educating students, particularly those from historically underrepresented groups, on how chemists begin to understand the problem of molecular recognition. There are three educational objectives that are integrated with each other, draw inspiration from the problem of sensing bacterial cell walls and are directed at teaching students what it means to be a scientist. The activities involve: (a) partnering with an expert in Early Childhood Education to develop and implement a new curriculum for grades K to 2 focused on how a chemist "senses" phenomena such as light and sound, (b) developing a program to enhance the chemistry background of K to 2 educators, allowing them to more readily approach science concepts when they start their own careers and (c) developing and implementing an introductory biochemistry lab in which undergraduate biochemistry majors use problem-based learning (PBL) to understand how concepts in molecular recognition are used in antibiotics that target the destruction of bacterial cell wall.
Organisms from plants to humans take advantage of the strong polymer unique to the bacterial cell wall to recognize the presence of a bacterial cell. However, the molecular details of recognition are not well understood. This project involves the preparation of synthetic analogues of bacterial cell wall to investigate the binding events used by mammalian and fungal systems. The use of these systems allows a comparison of the solutions devised by nature to bind the highly conserved polymer that comprises the cell wall. In two objectives, this research determines the binding events that drive the recognition of bacterial cell wall fragments by innate immune human and fungus receptors. The principal investigator is using chemical synthesis to build modified, tagged versions of bacterial cell wall fragments that are used for the identification and characterization of the binding sites for these molecules and their respective receptors. Bacterial cell wall fragment binding proteins Cyr1p, Nod1 and Nod2, from yeast and humans are being used in the investigation. These proteins are structurally diverse and each has been shown to be stimulated by bacterial cell wall fragments. The principal investigator makes use of a dynamic approach in refining the rules for binding to bacterial cell wall fragments. Student and teachers in K-2 are involved in a new curriculum on chemical sensing and recognition.
