A key goal in the field of Biochemistry is to understand the chemical and structural properties responsible for molecular recognition. Our lab addresses these questions through studying protein energetics, dynamics, and structure. We use experimental and computational/theoretical approaches toward this end. The long-term goals of this research will aid in the development of novel protein engineering strategies and structure-based drug design efforts.
Single Domain Antibodies
The majority of antibodies found in Camelids (e.g. camel and llama) possess unconventional antibody structures (as compared to human antibodies) whereby the antigen recognition site is located on only a single heavy chain domain. This single domain (sometimes referred to as a nanobody) is capable of binding antigen with high affinity and specificity. This minimal antibody domain is of interest for therapeutic and diagnostic uses and provides an excellent model for investigating the mechanisms protein-protein interactions. We are currently investigating the molecular basis of antibody-antigen and antibody-hapten (low-molecular weight ligand) recognition. In addition, we are developing methods to engineer unique features/functions into single domain antibodies. This research requires the use of a variety of techniques (e.g., biophysical. structural biology, molecular biology).
Design and Engineering of Novel Protein Affinity Reagents
Antibodies, such as the single domain VHH antibody (shown above), represent a starting point for generating protein reagents with novel properties. Combinatorial approaches, such as phage display, and structure-based design provide methods generate proteins with tailor-made function. We are interested in developing proteins, such as antibodies, that have properties that would not normally be possible to generate using conventional techniques. One example includes protein switches, where a protein’s binding function can be engineered to be regulated in a ligand-dependent fashion (e.g., pH- or metal ion).
Early Stage Infectious Disease Drug Design/Development
In collaboration with the Hagen lab (NIU) we are interested in designing and characterizing small molecule compounds that capable of inhibiting critical pathways of infectious agents. We are currently targeting several enzymes of the MEP pathway.
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