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- Creators: Arizona Board of Regents
- Status: Published
complex therapy-oriented networks over the past fifteen years. This advancement has
greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a
mechanism that cells use to achieve a discrete number of mutually exclusive states in
response to environmental inputs. However, complex contextual connections of gene
regulatory networks in natural settings often impede the experimental establishment of
the function and dynamics of each specific gene network.
In this work, diverse synthetic gene networks are rationally designed and
constructed using well-characterized biological components to approach the cell fate
determination and state transition dynamics in multistable systems. Results show that
unimodality and bimodality and trimodality can be achieved through manipulation of the
signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to
communicate with each other.
Moreover, a synthetic quadrastable circuit is also built and experimentally
demonstrated to have four stable steady states. Experiments, guided by mathematical
modeling predictions, reveal that sequential inductions generate distinct cell fates by
changing the landscape in sequence and hence navigating cells to different final states.
Circuit function depends on the specific protein expression levels in the circuit.
We then establish a protein expression predictor taking into account adjacent
transcriptional regions’ features through construction of ~120 synthetic gene circuits
(operons) in Escherichia coli. The predictor’s utility is further demonstrated in evaluating genes’ relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks.
These combined results illustrate applications of synthetic gene networks to
understand the cell fate determination and state transition dynamics in multistable
systems. A protein-expression predictor is also developed to evaluate and tune circuit
dynamics.
The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application of novel analogs of Bexarotene (RXR agonist), MeTC7 (a new potent VDR antagonist), and vitamin D as possible therapeutics for cancer and Alzheimer’s disease.
Anatomical models have always been a mainstay of descriptive embryology. As the training of embryologists grew in the late 1800s, so too did the need for large-scale teaching models. Embryo wax models, such as those made by Adolf Ziegler and Gustav Born, were popular in the latter part of the nineteenth century and the early twentieth century as a way to visualize, in three dimensions, the fine detail of embryos without the aid of a microscope. While these models were found in many university laboratories, museums of science, and even expositions and world's fairs, they were anything but easy to make or obtain. Wax modeling required skill, patience, and specialized tools. Small laboratories with only one or two embryologists often found the prospect of wax modeling too laborious, too difficult, and too expensive to make the pursuit worthwhile. As an alternative, Susanna Phelps Gage, an embryologist at Cornell University, perfected a technique of using stacks of absorbent blotting paper rather than stacks of wax plates for constructing embryo models. She first demonstrated her blotting paper method to other embryologists at the annual meeting of the Association of American Anatomists in 1905 and later at the International Zoological Congress, held in Boston in August 1907.
As the third director of the Carnegie Institute of Washington s Department of Embryology, George Washington Corner made a number of contributions to the life sciences as well as to administration. Corner was born on 12 December 1889 in Baltimore, Maryland, near the newly established Johns Hopkins University. Although Corner was not exposed to science much in school at a young age, he developed an early appreciation for science through conversations with his father about geography and by looking through the family's National Geographic magazines.
Franklin Paine Mall was born into a farming family in Belle Plaine, Iowa, on 28 September 1862. While he attended a local academy, an influential teacher fueled Mall's interest in science. From 1880-1883, he studied medicine at the University of Michigan, attaining his MD degree in 1883. William J. Mayo, who later became a famous surgeon and co-founder of the Mayo Clinic in Rochester, Minnesota, was a classmate of Mall's. Throughout his studies at Michigan, he was influenced by Corydon L. Ford, a professor of anatomy, Victor C. Vaughn, a biochemist and bacteriologist, and Henry Sewall, a physiologist.
The goal of science education in the United States is promoting scientific literacy for all students. The goal necessitates understanding the nature of science-what science is as a body of knowledge, explanatory tool, and human enterprise. The history of science is one of the most long-standing pedagogical methods of getting at the nature of science. But scientific literacy also encompasses education in scientific inquiry, and in the relationships among science, technology, and society (STS), as well as fact and theory-based subject-matter content.