CAREER: Room Temperature Stabilization of Cellular Factories by Confinement: A Thermodynamic Approach

ABSTRACT: CBET-0644784 , U. Minnesota, Dr. A. Aksan

CAREER: Room Temperature Stabilization of Cellular Factories by Confinement: A Thermodynamic Approach

The goal of this CAREER project is to develop a highly integrated research and teaching program focused on the thermodynamics of stabilization of biological systems (proteins, biomembranes, and cellular factories). Cellular factories are bacteria, plant, or animal cells that are genetically engineered to produce specific proteins, or to perform complex chemical reactions.).

Preservation of biological systems at room temperature by confinement (by embedding in sugar glasses, or encapsulation in porous matrices) is emerging as a viable and economical alternative to traditional techniques that require cryogenic temperatures for processing or storage. Long-term room temperature stabilization of certain enzymes and proteins in silica matrix confinement has been possible. However, the same level of success could not be repeated for more sensitive proteins, or cellular factories. The reason for failure is not known. This is the driving force for the PI to develop his program.

Intellectual Merit: The research objective of this project is to establish the thermodynamics of room temperature stabilization of biological systems by confinement. This will be achieved by pursuing the following specific aims:

1) Establish the mechanism(s), kinetics and thermodynamics of damage to biological systems due to changes in water activity,

2) Establish the mechanism(s), and thermodynamics of room temperature stabilization of biological systems by confinement,

3) Develop a thermodynamic model for room temperature stabilization by confinement.

The integrated teaching objective of the proposal is to develop a novel, technology-based educational tool (the E-valuate Program), which is focused on increasing outreach and mentoring by increasing the exposure and involvement of undergraduate and high school students (as well as teachers) in scientific and engineering education and research activities. The objectives of this program are:

Broader Impacts: The biological confinement systems are used in biomedicine (as insulin secreting implants for diabetic patients), biotechnology (recombinant protein, and enzyme production), bioremediation (to clean up toxic waste, and pollutants), green chemistry, alternative energy generation (electricity and hydrogen production by bacteria), and as biosensors ('canary cells,' which can detect the presence of pollutants, viral agents, or toxic chemicals

The research activities proposed here combine experimentation with theoretical modeling from a multidisciplinary perspective through the collaborations the PI has fostered with the Departments of Mechanical Engineering, and Microbiology, the Biotechnology Institute at the University of Minnesota and the local industry. This creates a unique research and teaching environment for undergraduate and graduate students employed through this project.

The teaching program utilizes a very commonly available technological tool (a PC with an internet connection). This makes it easier for the PI to reach the underrepresented groups and geographically disadvantaged institutions. As part of the teaching plan, a combined undergraduate/graduate level course focusing on the applications of thermodynamic principles to natural phenomena will also be developed.