MAJOR RESEARCH INTERESTS
Project direction at IU School of Medicine:
1. Having developed an RNA coliphage display technology presenting library and peptides and knowing the crucial role played by the highly glycosylated spike (S) protein of both coronaviruses (SARS-CoV and SARS-CoV-2), the causative agent of human severe acute respiratory syndrome (SARS) disease in mediating infection, we will endeavor to engineer RNA Qβ phage to map and elucidate the S protein domains recognizing antibody and angiotensin-converting enzyme 2, lipoprotein and related host cell receptors (DPP4, CD147). Ultimately, the expected results will provide a better understanding of SARS pathogenesis, severity, evolution, and re-emergence, and reveal new avenues towards molecular diagnostic and therapeutic tools in coronavirus diseases monitoring and prevention.
2. The structural spike (S) glycoprotein, common to both SARS-CoV-1 and SARS-CoV-2, plays a pivotal role by mediating the host cell entry and inducing the production of neutralizing antibodies, and was used to develop the vaccines. A quantitative monitoring of host S-related antibodies in SARS-CoVs infections could provide this information, but this method requires lateral flow assay (LFA) testing, which is expensive and not always sensitive enough. Thus, alternative affordable and accurate COVID-19 antibodies (Abs) monitoring methods are urgently required. To address this urgent need, we propose to explore the feasibility, using a combination of S epitope peptides with the minor coat protein A1 of the evolutionary RNA phage Qβ displayed as reagents for biosensors development.
3. Currently available methods for detecting chemical and biological threat agents require a combination of sophisticated biochemical and biophysical tools each with substantial drawbacks. For example, detecting new virus outbreak requires sophisticated and costly analytical techniques that combine serology testing, polymerase chain reaction, protein mass spectrometry, and genome sequencing. Some threat agents act at a very small concentration, making them difficult to detect, or disappear in the host after action, making them very difficult to monitor. To bridge this gap, we have developed a synthetic biological technique to use RNA coliphage display as a biosensor toolkit to concentrate and detect biological and chemical threats. The Phage Qβ display of a library of peptides can be used to bind and concentrate a broad range of organic (virus glycoproteins, virus-related antibodies, toxins of harmful algal blooms and bacteria) or nonorganic molecules (gold, zinc, cobalt, or peroxide a precursor of explosives like TATP). A repertoire of peptides that bind TATPs and other explosives or precursors can be developed to help warfighters by neutralization assay. The repertoire can be other means of control and security for the Department of Homeland Security.
4. This can go from single atoms to a wide range of proteins (the antibody binding domains of the spike protein of both coronaviruses, Ebola, Yellow fever, Zika viruses, and the antigenic protein of VEEV) in the nanomolar range in real time. Qβ can present foreign appropriate affinity peptide(s) on its surface and serve as a toolkit that concentrates and detects biological and chemical threats (immobilized/in suspension) in real time.