The CHOg2p project is possible due to the Research Infrastructure Improvement Track-2 Focused EPSCoR (Established Program to Stimulate Competitive Research) Collaborations (RII Track-2 FEC) award and aims to bring together Clemson University, University of Delaware, Tulane University, and Delaware State University in order to develop new biological approaches to better understand the Chinese hamster ovary (CHO) cell line, which is used to manufacture most biopharmaceuticals. CHO cells are used to manufacture more than 50% of biopharmaceuticals, and products from CHO cells have global sales over $70 billion per year. Some biopharmaceuticals produced using this cell line include infliximab to treat Crohn's disease and erythropoietin (EPO) to treat severe anemia. CHO cell lines provide a unique opportunity to quantitatively address the complex interactions between the genome and phenome because these cells can be cultured in very tightly controlled environments (bioreactors) to generate variable phenomes due to genome instability.

A lack of understanding of the fundamental link between genome stability and the phenome significantly limits the ability to improve cell lines and ultimately increase product yields. This project will generate foundational knowledge linking the genome (what is in the chromosome or DNA) to what is observed (the phenome) and insight into the basis for genomic instability in CHO cells. This award provides the opportunity for investigators with complementary expertise to collaborate in advance of developing bio-manufacturing knowledge. Additionally, the project will mentor four early-career tenure-track underrepresented minority (URM) faculty and train postdoctoral scholars and graduate and undergraduate students.

As a critical part of this project, Dr. Harcum’s lab acquired the first ambr^®250 at an academic institution in the U.S. This advanced instrument provides high precision control of the environment necessary for mammalian cells, including CHO cells, to produce biopharmaceuticals. With the ambr^®250, the team is able to explore a wide range of CHO cell culture conditions with scalability through both benchtop and large stirred tank bioreactors used in industry (10,000-L).

The project’s overall vision is to: 1) expand the research infrastructure in participating institutions; 2) build individual and collective competence graduate students in genome-phenome knowledge and CHO cell cultivation and engineering; 3) share genome-phenome knowledge and tools that could be applicable to any other organism whether or not it has issues with genome stability; 4) broaden and foster the participation of tenure-track early-career underrepresented minority (URM) faculty members; and 5) provide research experiences for URM students and establish student exchanges among the participating EPSCoR jurisdictions.