Page 6 - CEMS News Summer 2020

FACULTY NEWS
CEMS faculty tackling COVID research
Hackel and Hu are pursuing creative virus solutions.
Ben Hackel
labmates. An initial panel of engineered proteins exhibit binding to the viral target, which is encouraging but
still requires substantial further development. The team recently received a pilot grant from the Institute for Engineering in Medicine to support one element of the research.
Wei-Shou Hu
Ben Hackel
Researchers in the lab of Associate Professor Ben Hackel are engineering proteins to inhibit the emergent coronavirus from entering cells. The proteins aim to selectively bind to the complex molecular machinery required for cellular entry thereby preventing viral infection. To engineer molecules with specific binding potency
to the intended targets,
The graduate students who
have been using a synthetic
biology approach to develop
a new way of producing
influenza virus and an adeno
associated virus in Wei-Shou
Hu’s laboratory, including Zion
Lee, Thu Phan, Min Lu and
Qian Ye, have joined forces in
the past two months to create
cell lines that can produce
engineered spike proteins of
the SARS-CoV-2 virus. The
spike protein is a very large,
structurally complex protein
and forms a trimer that is more than three times larger than human antibodies. It is embedded in the surface of the virus membrane, so scientists are very interested in exploring its structure, functions and immunogenicity.
However, the complex protein is also very difficult to produce. The team has generated Chinese hamster ovary (CHO) cell lines which can stably produce the
wild type and mutant proteins. Besides generating the spike protein needed for the research in the laboratories of Hu and his collaborator, the cell line will be made available to collaborators as well as the broader scientific community in general to advance devising means to fight the pandemic.
researchers are using a technology platform previously developed in the Hackel
lab for engineering molecular imaging diagnostics and cancer therapeutics. In this technology, designed sets of billions of protein variants are produced by yeast cells and tested for target binding via a technique called flow cytometry.
The most effective binding proteins are isolated while still tethered to their host yeast, whose genetic material is then sequenced to identify the functional protein. The lab previously optimized the libraries of protein variants for binding capacity across an array of therapeutic and diagnostic targets. Thus, researchers were poised to apply the technology to the emergent virus.
A collaborative team with Jonathan Sachs (Biomedical Engineering), David Ferguson (Medicinal Chemistry), and Alon Herschhorn (Infectious Diseases and International Medicine) identified and modeled the most compelling molecular targets to hinder coronavirus infectivity and set up assays for downstream evaluation.
Graduate students Sarah Whillock, Patrick Lown, and Daniel Tresnak, as well as research scientists Crystal Dyer and Mani Vunnam, have diligently performed the laboratory research along with assistance from additional
Wei-Shou Hu
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