Dr. Wolfgang Banzhaf awarded an NIH grant

Abstract:

 

"A major challenge of translating synthetic biology approaches to clinical treatment is the need to improve  the communication with biological circuits in vivo. One example is the need to manipulate the amino acid sequence of peptides to improve their function as bioactive molecules. We developed a new  machine learning tool based on “genetic programming” that can assist in designing new proteins and  bioactive peptides. This new technology, termed Protein Optimization Evolving Tool (POET), generates  models that describe the relationship between a peptide and its respective activity. Through cycles of function measurements and model improvement, we can generate peptides with substantially improved function. In this project we seek to improve, test and implement this approach for three related, yet independent goals. First, we will deploy POET to develop an ultrasensitive peptide-based imaging agent for MRI based on proton exchange. Our preliminary data show that through only few cycles of peptide evolution we surpassed the state-of-the-art similar peptides. Second, we shall use a similar approach to develop a novel MRI imaging probe based on T1 relaxation. In particular, we will use metabolic engineering approaches to express and load the peptide with Lanthanides, and the POET algorithm to improve its function iteratively. Lastly, we shall employ the POET tool to discover new peptides for drug and gene delivery. A novel platform for gene/drug delivery will be used to test the efficiency of the resulting peptides. All three aims will start with computational design of peptides followed by in vitro testing and several cycles of peptide evolution until the ultimate peptides are identified. We shall demonstrate the utility of the obtained peptides in a clinically relevant question in an in vivo model, followed by non-invasive imaging. This approach can open up new avenues for developing powerful bioactive peptides to solve critical biological questions and to create new diagnostic/therapeutic approaches to currently devastating human diseases."