Craig Barry, Computational Modeling

During my undergraduate studies in chemical engineering and for a short stint in industry, I largely gained exposure to the world of inorganic commodity chemicals. Working as an engineer, I developed an interest in dynamic modeling for design and optimization. I liked the idea of mathematical modeling for rational design of industrial cell lines and bioprocess unit operations. That quickly grew into a passion during my postgraduate research on tetanus vaccine bioprocess optimization at the University of Queensland.

Substantial improvements to biopharmaceutical cell-culture technologies require intelligent engineering of robust cell lines that are suited to unique bioreactor environments. Using a proteomic-centered framework, my project aims to build a computational model that investigates the biological mechanisms of Chinese hamster ovary (CHO) cell proliferation and programmed cell death. Dynamic modeling is used to give order to complex data sets and to account for noise, which is inherent to cellular biology. Ultimately, in silico interrogation of a model offers a means to experiment with rewired CHO cell biology, enabling future development of more robust manufacturing strains.

CBI greatly facilitated my ability to exercise my passion in the biopharmaceutical industry through an engaging doctoral project with Thermo Fisher Scientific. With the company’s guidance and exposure to the biologics industry, I have gained perspective on what the near future may hold for that industry and how I can play a part in it as an engineer. I’m eager to gain industry experience through an internship with Thermo Fisher Scientific.

I thoroughly enjoy the continual academic challenges of a PhD project and the freedom of thought that the project facilitates.

Michael MacDonald, Cell Line Development

Cell death often is considered to be inevitable and unpredictable in upstream production, but it is controlled by deliberate decision-making signaling pathways within cells, most notably during apoptosis. My CBI colleagues and I have published a review describing the work in this area (3). My project focuses on using CRISPR technologies to incorporate rational modification of critical points in apoptotic pathways to create hardy cell lines that are resistant to process stress. The ultimate goal is to develop cells that live longer and are more productive and efficient than currently available cell lines, reducing media costs and increasing titer.

I am eager to find a niche between the theoretical and practical aspects of the life sciences. Having worked as both an academic researcher and a production scientist, I considered the opportunity to combine these two aspects in a doctoral setting to be an ideal first step into R&D.

In addition to providing technical knowledge and experience with the latest technologies, working in the space between academia and industry has enabled me to encounter and negotiate unique challenges. Through those challenges and with the support of mentors from many walks of life, I have cultivated a skill set that will prove invaluable in my future endeavors.

CBI also has enabled me to work in different physical and professional spaces and to meet and work with groups of amazing people. Over the course of my doctoral program, I have been surprised routinely by the diversity and skills of the people with whom I work. I believe that it was a tremendous insight by the ARC and Thermo Fisher Scientific to commit to this center and that their investments will yield promising results.

Matthias Nöbel, Perfusion Culture

High cell densities often are linked directly to increased overall process productivity. Because of single-use technologies and improved process monitoring tools, continuous perfusion systems are gaining in popularity. Compared with traditional discontinuous operations, increased cell densities and changes in cell environments are making new metabolic demands of perfusion cell systems. My project uses a systems-biology approach to analyze cellular proteins and metabolites under different conditions to understand metabolic changes. Ideally, my findings will be translated into approaches that maximize the metabolic performance, stability, and product yield of perfusion culture systems.

Unlike other CBI entrants, my experience with the biopharmaceutical industry was limited. Having the opportunity to explore beyond an academic environment and gain industry insight was one of the major draws for me to join the center.

For my industry placement, I spent time at Thermo Fisher Scientific’s R&D facility in Princeton, NJ, which specializes in manufacturing a wide range of biopharmaceutical proteins. From the start, I learned about the differences between academia and industry. Starting with the size of teams and operational units and stretching to the work structure itself, my activities at Thermo Fisher Scientific differed substantially from my work at a university.

Because of my placement, now I understand the distinctive challenges faced in a commercial environment: documentation, scale-up, and simultaneous management of departments, customers, and colleagues. The guidance of experts in those fields helped me develop skills I needed to solve new problems quickly and effectively.
The perspective I am gaining makes me feel well prepared for what lies ahead of me. My daily work at the university has gained a boost as well thanks to the techniques and structures I learned during industry placement.

Kristina Pleitt, Continuous Chromatography

Market pressure for fast, cost-effective production of clinical material has increased outsourcing to contract development and manufacturing organizations (CDMOs). To meet client expectations, CDMOs seek to offer robust approaches for development, production, and testing of products with competitive pricing and timelines.

My project focuses on the potential of continuous downstream processing for improving manufacturing efficiency and flexibility. Using process-simulation software, I determined the most favorable situations for implementing continuous and semicontinuous downstream processing for monoclonal antibodies (MAbs) (4).

The common thread among MAb downstream platforms is product capture using protein A, which makes conversion from batch to continuous operation relatively straightforward. But CDMOs work with a wide range of proteins, and without a suitable affinity resin, purification is challenging. I am investigating continuous processing strategies for non-MAb recombinant proteins.

After my undergraduate work, I joined a process development group at a newly formed CDMO. I was learning constantly and enjoyed the work. It is rewarding knowing that your work contributes to patients’ receiving the treatments they need. I could not imagine stepping away from my job, but I was interested in pursuing a doctoral degree and knew that doing so would help my career. When a former manager told me about CBI, I jumped at the opportunity.

CBI’s partnership between academia and industry allows me to remain active in both areas. More important, the research is relevant and something that I want to study.
I’ve grown personally and professionally through mentorship from CBI’s researchers and industry partners. I appreciate how CBI projects are focused on issues that are applicable to the biopharmaceutical industry and how the program emphasizes strong research principles as well as several “soft skills.”

It can be challenging to balance full-time doctoral work with a full-time job, but I’m fortunate to have a supportive network through CBI and my company, Thermo Fisher Scientific. I’m thankful to work in such a rewarding field.

Sathish Nadar, Membrane Technology

The biopharmaceutical industry has been conventional in its approach to developing production processes for recombinant therapeutic drugs, mainly because of a highly regulated environment. However, surges in demand for this class of molecules and the advent of biosimilars have forced the industry to seek out innovative and cost-effective solutions to remain competitive. My ambition is to help find beneficial solutions for both patients and the industry.

Biologics manufacturers traditionally have used resin-based chromatography to purify protein therapeutics. Despite being a powerful technology, resins are expensive, work slowly, and require elaborate cleaning and associated validation. Because of its faster operation and its availability in single-use options, membrane technology represents an alternative to resin-based chromatography. My doctoral project assesses the performance and potential cost benefits of membrane-chromatography processes.

I was introduced to CBI by a colleague at my past organization who had joined the program as a postdoctoral researcher. At that point, I was not sure of taking up this PhD program because for me it meant leaving a comfort zone within a well-organized R&D department in a multinational biopharmaceutical industry and travelling 6,000 miles away from my hometown. However, after working for four years in bioprocess R&D, I started to feel a stagnancy in terms of knowledge and an urge to take up something more challenging. It did not take long to convince myself to undertake doctoral study, which I would rather call my “big promotion.”

At CBI, I still feel that I am part of a well-structured industry project mentored by highly experienced leaders, but now I am the one making the critical decisions and getting the opportunity to learn both technical and project- management skills. I do sometimes feel exposed and challenged in front of the vast experience of industry mentors, but at the same time, I am protected when my academic supervisor guides me through difficult times in my project and helps me learn from my mistakes. Currently in the second year of my degree program, I have no regrets about leaving a job for this program because this journey has been both enriching and exciting.