DNA four-way junctions (also known as Holliday junctions) are the primary structural intermediate during recombination, an important process responsible for biological evolution and maintenance of genomes. These junctions arise from the assembly of four nucleic acid strands to produce double-helical regions extending from a central point. Although much progress has...
Paper-based microfluidic assays, like the common pregnancy test, allow for rapid screening at the point- of-care at low cost and with no instrumentation. Fabric has many similar properties to paper, but is more flexible and durable, making it a promising option for use in a variety of diagnostic and screening...
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AndrewKarplus, Committee Member, representing the Department of Biochemistry and Biophysics
Intrinsically disordered proteins (IDP) are a class of proteins that lack a three-dimensional structure and their prevalence and diverse functions in the cell have only been discovered relatively recently. The intermediate chain (IC) subunit of the microtubule motor protein complex dynein contains an N-terminal disordered region, N-IC, which is central...
The ferritin-like superfamily (FLSF) of proteins is composed of a wide variety of functionally diverse proteins involved in oxygen dependent metal-mediated electron transfer reactions. Their biological importance is exemplified by the fact FLSF proteins are found in almost every organism from all three domains of life. Their functions range from...
Contact of blood with the surfaces of synthetic materials is associated with spontaneous protein adsorption, initiating platelet aggregation, the coagulation cascade, and the eventual development of a stable clot. Current therapy to inhibit implant-induced thrombosis is life-long administration of systemic anticoagulants. An alternative to the systemic administration of anticoagulant drugs...
The halogen bond is a non-covalent, stabilizing interaction analogous to a hydrogen bond in which an anisotropically polarized halogen atom interacts
electrostatically with a Lewis base. Until very recently, the ability of halogens to form these stabilizing interactions in biological macromolecules was all but unknown, but
examples of halogen bonding...
Cells represent microcosms of spatial and temporal structural organization, with the achievement of internal spatial organization relying upon a collection of macromolecular motor complexes to transport and localize components throughout the cell. Cytoplasmic dynein is one such motor complex, and is the principal ATP-dependent motor for retrograde transport along microtubules...
Altogether, this dissertation highlights the value of mass spectrometry-based analysis of intact proteins for solving problems related to understanding disease mechanisms and developing new therapeutics.
Mutations to the antioxidant enzyme Cu, Zn Superoxide Dismutase (SOD1) perturb protein structure in vivo to cause 2-5% of amyotrophic lateral sclerosis (ALS) cases. Metal-deficient...
Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by the progressive degeneration of motor neurons. Dominantly-inherited mutations to the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) cause 3-6% of all ALS cases. The complete mechanism behind the toxicity of mutant SOD1 remains unclear, although significant evidence points to aberrant or...
Cell motility and invasion are important for development, immunity, wound healing, and tumor cell metastasis. Cells on two dimensional substrates migrate in three steps: protrusion of the front end, translocation of the cell body, and retraction of the rear end. For cells to migrate efficiently, these steps need to be...