Bacteria represent the most abundant form of life on Earth and have evolved to successfully colonize nearly every environmental niche. In doing so, bacteria predominately form multicellular communities known as biofilms, resulting in increased resilience, persistence, and emergent behaviors. Consequently, biofilms present an attractive target for engineering and synthetic biology,...
The extracellular matrix (ECM) is a masterwork of biology, and its development was a key part of the transformation from monocellular to multicellular life. With an ECM, cells acquired the ability to cooperatively build a dynamic support network that facilitated their movement, specialization, and communication. This ECM is a hierarchical...
Tailoring the design of surfaces and interfaces with nanoscale features has the ability to significantly impact biological functions for a swath of applications including drug delivery, structure assembly, and biomedicine. For example, creating spatially defined nanoscale patterns has been known to contribute to changes in cellular architecture and mechanical properties,...
Cellular translation is responsible for the synthesis of proteins, a highly diverse class of macromolecules that form the basis of biological function. In Escherichia coli, harnessing and engineering of the biomolecular components of translation, such as ribosomes, transfer RNAs (tRNAs) and aminoacyl-tRNA synthetases, has led to both biotechnology products (i.e.,...
Protein-based biomaterials are widely used in biomedical applications and mechanical support because of their novel structural flexibility, biocompatibility and mechanical properties. Protein-based biomaterials outperform traditional synthetic materials in various environments as traditional materials lack the diverse chemical functionalities that proteins offer. Novel bioinspired techniques such as directed evolution offer the...
Protein-protein interactions are ubiquitous in living systems, and mediate important cellular processes from decision making to immunity against pathogens. Furthermore, protein-protein interactions are key to many protein therapeutics, pathogen diagnostics, and numerous synthetic biology applications. As a result, there has been significant effort to develop methods to express potential protein...
Breakthroughs in large-scale biological data collection have resulted in a wealth of -omics (genomics, metabolomics, etc.) datasets in the literature. However, the development of appropriate computational techniques for their analysis is lacking, yet crucial for fully extracting the rich information contained in these datasets. The work in this dissertation describes...
Advances in methods to sequence and manipulate DNA have enabled systems that enzymatically encode information in cellular DNA in situ. These systems, broadly categorized as molecular recorders, couple signals of interest to the expression of DNA modification enzymes, resulting in signal-dependent changes in DNA sequence. While a variety of molecular...
Three in ten people worldwide lack access to a safely managed source of drinking water, with one in ten lacking access to a drinking water service altogether. This is projected to worsen in the coming years as climate change, infrastructure degradation, and poor governance work to further increase global water...
Ensuring adequate water quality is essential for human health and for effective allocation of resources in agriculture, energy, and manufacturing. However, the current state-of-the-art for water quality testing requires expensive equipment and technical expertise to analyze samples and takes days to obtain results from off-site labs, making it inaccessible to...
SAMDI-MS, which stands for self-assembled monolayers (SAMs) for matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS), is a powerful tool that has enabled the development of novel high-throughput screening and experimentation methods for decades. SAMDI-MS works by immobilizing analytes to functionalized SAMs prior to MS analysis and is capable of...
No two cells in a population are identical to each other. Cell populations are almost universally heterogeneous, with their heterogeneity or variability often underlying complex emergent behavior and phenotypes. Heterogeneity presents a challenge to the discovery, characterization, and control of multicellular systems. Heterogeneity exists across multiple scales, ranging from the...
Chimeric antigen receptor (CAR) T-cell therapies marry advances in cellular engineering with personalized medicine to provide patient-specific, targeted cancer treatments. Though current CAR T-cell therapies successfully target blood cell cancers, treating solid tumors has proven to be more challenging. Solid-tumor CAR designs must overcome several challenges, including tumor microenvironment barriers...
Biological experiments involving the manipulation and analysis of cells have always strived towards greater precision and resolution. Recent advances in micro and nanotechnology have improved the precision of manipulation and the resolution of analysis down to a single cell, thus opening new avenues of investigation. These advances have added a...
Current technologies capable of establishing bioresorbable orthopedic fixation devices and stents have broad utility for biomedical applications to improve constructive tissue remodeling. Recent studies and investigations on bioresorbable conductors, semiconductors, dielectrics, and polymer substrates offer a promising opportunity to propel the existing non-degradable bioelectronic devices to the promising bioresorbable electronics,...
Biological therapeutics have revolutionized the way we treat cancer due to their ability to target tumors discriminately, leaving healthy cells unaffected. However, our inability to tailor the structure of biologics may hamper their optimization for efficacy. This lack of programmability contributes to factors such as immunogenic responses, inability to penetrate...
A major distinction among different skeletal muscles in the human body is the number, size, and arrangement of its cells, referred to as a muscle’s architecture. Muscle architecture is indicative of a muscle’s ability to contract and produce force and, like muscle function, is plastic. While neuromuscular plasticity is the...
The Escherichia coli ribosome is a molecular machine capable of sequence-defined polymerization of -amino acids into proteins, a feat unmatched by any other current synthetic catalyst. It is complex in its structure, comprised of 3 RNA parts (the 5S, 16S, and 23S ribosomal RNAs) and 54 ribosomal proteins (r-proteins). Efforts...
By 2030, up to half of the world’s population is projected to suffer from water insecurity: a chronic scarcity of potable water due to rapidly warming temperatures, increased agricultural demand, and pollution. The health impacts of contaminated water are profound: hundreds of thousands of global deaths each year are ascribed...
While metabolic engineering can enable the sustainable bioproduction of new materials, efforts are often impeded by pathway bottlenecks. To mitigate the effects of toxic or reactive intermediates and resource competition resulting from heterologous pathway incorporation, bacterial microcompartments (MCPs) have recently been considered for engineered compartmentalization in bacterial host organisms. MCPs...