Calin Plesa, an assistant professor at the University of Oregon’s Phil and Penny Knight Campus for Accelerating Scientific Impact, has been awarded a $2.1 million grant from the National Institutes of Health’s Director’s New Innovator Award Program for his project, “Proteome Scale Multiplexed Generation of Recombinant Antibodies.”
A synthetic biologist whose research interests lie at the intersection of biochemistry, protein engineering, microbiology, synthetic biology, genetics, and technology, Plesa is improving and lowering the cost of gene synthesis, which is used in nearly all areas of life sciences research including studies on how mutations influence disease development and the development of new therapeutics.
Plesa’s NIH project addresses the growing need for antibodies for both basic research and therapeutics. Currently there are major limitations in the availability of antibodies and our ability to develop new antibodies. This research aims to create a platform for generating and testing antibodies for every protein present in an organism, around 20,000 in humans. It promises to be an order-of-magnitude improvement over current high-throughput methods of generating antibodies, which are slow, laborious, require automation, and are dependent on antigen availability.
Many of the techniques and studies used over the past few years have been limited by the availability of quality antibody reagents, which are still generated one-by-one for each antigen target and the lack of antibody sequences available. Concerns have also been raised about the equality and reproducibility of current commercial antibodies. Furthermore, many new techniques have been developed which study many proteins simultaneously rather than one-by-one, but these have been hampered by the lack of protein binders for many target antigens.
“There is an urgent need to develop methods that are capable of generating novel antibodies and binding proteins against all target antigens,” Plesa said.
Researchers will initially target antigens among the proteins expressed in humans and zebrafish and will screen these for cross reactivity. The results could eventually help dramatically reduce the cost of antibody generation and lead to the rapid creation of large libraries of verified antibodies.
“Successful completion of this work will provide a treasure trove of sequence-verified, high-specificity antibodies, and binding proteins,” Plesa said. “Given the ubiquitous nature of antibody reagents, this research could have a significant impact on broad areas of basic and clinical research.”
