Proteins represent a critical class of biomolecules, universally employed by all living organisms to fulfill essential structural, functional, and enzymatic roles necessary to support life. In nature, these polymers are composed generally of twenty natural amino acid (AA) building blocks, which can be modified with covalent adducts known as post-translational...
Platelets are circulating anucleate discs derived from megakaryocytes, and play major roles in hemostasis, inflammation, thrombosis, and vascular biology. Multi-phase culture systems for inducing in vitro platelet production from mature megakaryocytes have been explored to allow progenitor expansion, megakaryocyte maturation, and promotion of platelet formation and shedding. In this thesis,...
End-stage renal disease, or kidney failure, can result from acute kidney injury or sustained kidney damage in the form of chronic kidney disease. As the prevalence of end-stage renal disease continues to rise, the gold-standard treatment—kidney transplantation—is increasingly restricted by the shortage of transplantable donor kidneys. Bioengineered kidney tissues may...
The work in this thesis focuses on computational methods for the identification of novel enzymatic pathways. In particular this work focuses on the utilization of the Biological Network Integrated Computational Explorer (BNICE) software suite to predict de novo enzymatic pathways for the production of commercially relevant compounds and on improvements...
Currently, platelet transfusions, possessing profound clinical importance in the clotting of blood and healing of wounds, are entirely derived from human volunteer donors. This approach is limited by a 5-day shelf life, the potential risk of contamination, and differences in donor/recipient immunology. In vivo, platelets are formed when bone marrow...
More than half of proteins in humans are modified with carbohydrates in a process called glycosylation, yet this process remains poorly understood even though approximately 1% of the expressed human genome encodes biosynthetic machinery for glycosylation. Unlike genomics and proteomics where high throughput tools are now routinely used to generate...
Biochips and high-throughput screening methods are powerful tools for studying biological processes. The combination of peptide arrays and SAMDI mass spectrometry incorporates these tools to study a broad range of biochemical transformations, including enzyme activities, to provide valuable information on substrate recognition and guide the development of diagnostic and therapeutic...
Recent advances in combinatorial chemistry, synthetic biology, and ‘omics’ research require high-throughput methods for performing and analyzing thousands to millions of reactions in one day. However, it is a challenge to engineer high-throughput systems that can autonomously conduct and analyze such a large number of reactions in a generalizable and...
Millions of years of evolution have produced fascinating biological materials and structures that are optimized to perform a wide spectrum of functions essential for the survival of organisms. These biological materials have been intensively studied in order to decipher the intricate interplay between their superior material properties and structural design...
Built from non-covalent interactions, supramolecular biomaterials are highly dynamic and tunable, and recent work has shown that they are uniquely capable of mimicking functional biological structures. In this work, supramolecular biomaterials built from self-assembling peptide amphiphiles (PA) were investigated with the goal of precisely tuning their cohesive interactions to optimize...