From a simple blood draw, Krishanu Saha, a researcher in WID’s BIONATES research group and assistant professor of biomedical engineering, could enable doctors to create stem cells to develop drugs personalized to their patients.
Stem cells have the potential to develop into many different cell types, which makes them ideal for a variety of medical research projects.
The evolution of synthetic DNA sequences in human stem cells could catalyze the advanced manufacturing of stem cells for a variety of applications, ranging from tissue engineering to personalized medicine.
Currently, genetically engineering stem cells is expensive and difficult, which makes manufacturing them an issue.
“The primary way in which biologists have been modifying stem cells is to cut specific spots in the genome and then add foreign DNA,” Saha says. “Then, biologists can insert new sequences or correct problematic mutations.”
This method of integrating foreign DNA is inefficient in human stem cells, particularly on a scale large enough to query the multitude of DNA sequences that may help in the advanced manufacturing of these cells. Typically, researchers anticipate that millions to billions of cells are necessary for therapeutic applications or disease modeling (…)
The research is inspired by a chemical engineering idea called “directed evolution,” Saha says. Just as a chemical engineer can directly evolve enzymes in bacteria for particular purposes — for example, evolving low-temperature enzymes for household laundry detergents — biomedical engineers can direct evolutionary processes on human proteins within stem cells for a particular application (…)
And beyond hands-on experience, Saha intends to emphasize the importance of public policy and bioethics through his training modules. He says focusing on public points of controversy, such as stem cell research, will allow the next generation of scientists to better reflect on the complex ways in which science and society interact in biomedical research.
Human stem cells provide an attractive, patient-matched source for generating many tissues found in the body, but controlling stem cells in culture remains a key challenge. To meet this challenge, this proposal seeks to develop and apply synthetic biology tools in order to dissect and precisely control the complex molecular signaling processes that determine stem cell behavior in culture. Synthetic biology is an emerging biotechnology field that combines elements of engineering, mathematics, chemistry, and biology to synthesize novel systems from characterized biological components. Applying new synthetic biology tools in human stem cells to control cell behavior would enable advanced manufacturing of patient-specific tissues and cells for disease modeling and drug discovery applications.
This proposal outlines a novel approach to convert natural signaling components in human stem cells to synthetic, bioorthogonal ones.
The approach relies on producing mutations in cells at defined genomic locations. Such an approach allows for the formation of libraries of mutant cells that can be selected for particular functions.
The proposal focuses on a fundamental barrier to establishing a robust stem cell tissue engineering and bioprocessing industry ? manipulating cell signaling pathways when stem cells grow in culture and come together with other cells and materials.
The research will be integrated into education by developing and disseminating course modules demonstrating the importance of cross-disciplinary training in stem cell biology, engineering and bioethics for postgenomic approaches to human biomedicine. The proposal to incorporate underrepresented students into the research laboratory and to advance new curriculum will help to develop the next generation of students trained at the stem cell biology-engineering interface.