Impact Highlights

Aralez Bio. JIMEM support laid the foundation for Frances Arnold Lab's spin-out company Aralez Bio. Founded in 2019, Aralez Bio engineered tryptophan synthase enzymes to prepare non-canonical amino acids for a wide range of research and therapeutic applications. Caltech postdoc Dr. Tina Boville was awarded a Cyclotron Road Fellowship to found Aralez Bio in the San Francisco Bay Area. The company is already supplying products to customers.

Protomer Technologies. In 2015, Alborz Mahdavi, who earned his Ph.D. in bioengineering in the Tirrell Laboratory, founded Protomer Technologies to create protein therapeutics that can be activated by small-molecule disease markers to achieve autonomous control of drug dosage. In 2021, the Pasadena-based company was acquired by Eli Lilly. According to the Lilly announcement, the "potential value of the transaction is over $1 billion, with successful achievement of future development and commercial milestones." An early development target for Protomer has been a glucose-responsive form of insulin.  Ruth Gimeno, vice president of diabetes research and clinical investigation at Lilly, is quoted as saying, "Glucose-sensing insulin is the next frontier and has the potential to revolutionize the treatment and quality of life of people with diabetes by dramatically improving both therapeutic efficacy and safety of insulin therapy."

More than a dozen patent applications have been filed in the last ~5 years and several patents have been published and issued.

Filed IP covers a diverse array of topics, including:

• Methods for therapeutic particle delivery to the cornea
• New insulin variants with altered and potentially useful biophysical properties
• Engineered tryptophan synthase enzymes to prepare non-canonical amino acids for a wide range of research and therapeutic applications
• Acoustically responsive gas vesicles that would allow clinicians to use ultrasound as a means to image and subsequently, trigger drug release
• Methods of microbial enrichment, quantitative sequencing, and 3D imaging to enable the study of multi-kingdom microbiomes in clinical specimens
• An instructional device for point-of-care sample handling
• Methods for rapid antibiotic susceptibility testing

JIMEM has supported 32 fellowships, attracting new talent to Caltech's PhD program. The JIMEM Fellows are all students who are passionate about pursuing translational medicine as part of their PhD studies. JIMEM has also supported the research (stipends and/or research supplies) of more than 62 research students and postdocs over the last ~5 years.

The JIMEM-supported trainees have been highly successful. They have won numerous awards, including the Intelligence Community Postdoctoral Fellowship, the Baxter Young Investigator Award, Caltech's McCoy Award, Caltech's Reddy Award, the New England Biolabs Passion in Science Award, a Caltech Caldwell CEMI Graduate Fellowship, and a Cyclotron Road Fellowship. JIMEM support is acknowledged in more than 11 Caltech doctoral theses.

JIMEM seed funding has led to numerous large federal grants and contracts and private funding for the Caltech investigators. Federal funding includes a $1.2M NIH R01 grant, a collaborative NIH RC2 grant, an exploratory NIH R21, an NIH BRAIN initiative grant, and a $1.84M DoD contract with the Defense Threat Reduction Agency (DTRA). Funding from companies includes a $1.5M University Partnership Initiative with Dow Chemical and a $200K Amgen Chem-Bio-Engineering Award. In addition, numerous private foundations, such as the Kenneth Rainin Foundation and the Patten Charitable Fund, have supported work made possible by seed funding from the Jacobs Institute.

Publications supported by JIMEM have spanned the fields of biochemistry, chemical engineering, biological engineering, biophysics, epidemiology, molecular biology, diagnostics, proteomics, and materials science.

Key areas of focus have included:

• Innovative Methods in Protein Engineering: Several studies explore high-throughput screening methods for enzymes, site-specific incorporation of noncanonical amino acids, and the evolution of proteins like green fluorescent protein. This research aims to expand the toolkit for modifying and understanding proteins, with applications in understanding protein function and designing new biomolecules.
• Materials Science and Nanotechnology: Research on photoreactive cell-adhesive proteins, mechanically tunable thin films, and the interaction of polymers with biological systems exemplify the cross-disciplinary work at the interface of materials science and biology. These studies have implications for medical device design, tissue engineering, and drug delivery systems.
• Enzyme Engineering and Directed Evolution: A significant portion of the research focuses on engineering enzymes for novel reactions, including expanding the capabilities of cytochrome P450 enzymes, development of artificial metalloenzymes, and creation of biocatalysts for organic synthesis. This work pushes the boundaries of what is chemically possible in living systems and has broad implications for synthetic biology, pharmaceutical development, and green chemistry.
• Medical and Diagnostic Applications: Several publications delve into medical applications, including the development of MRI contrast agents, methods for rapid antibiotic susceptibility testing, and studies on tissue mechanics relevant to biomedical devices. This research is crucial for advancing diagnostic techniques, understanding disease mechanisms, and developing new therapeutic strategies.
• Public health and COVID-19 Research: Recent studies focus on SARS-CoV-2, addressing challenges in viral detection, understanding viral load dynamics, and evaluating testing methodologies. This research is vital for informing public health strategies and improving diagnostic tools in response to the COVID-19 pandemic.

Overall, this body of work represents a concerted effort to harness biochemical and engineering principles to address fundamental questions in biology, create innovative materials and diagnostic tools, and develop new therapeutic strategies.

Recent Clinical and academic collaborations have included Cedars-Sinai Medical Center, University of Chicago Medicine, Argonne National Laboratories, Warwick University, Queen's University Belfast, Vanderbilt, University of Iowa, the University of California–Los Angeles, the University of Oregon, and numerous collaborations with other labs at Caltech. Public Health collaborations have included Pasadena Public Health Department and the Long Beach Public Health Department. Industry collaborations have included Zymo Research and Abbott.