Molecular Biology Commons^™

Connecting Motors And Membranes: A Quantitative Investigation Of Dynein Pathway Components And In Vitro Characterization Of The Num1 Coiled Coil Domain, Bryan J. St. Germain

Masters Theses 1911 - February 2014

In the budding yeast, Saccharomyces Cerevisiae, dynein, a minus-end directed motor, is involved in nuclear migration and proper orientation of the mitotic spindle during mitosis. Our lab has developed a model that involves the loading of cytoplasmic dynein onto the plus-end of astral microtubules through interactions with Pac1/LIS1 and Bik1/CLIP-170. Dynein is then delivered to the cell cortex and anchored through a cortical receptor protein, Num1. Num1 is a 313KDa protein that localizes to the cell cortex and is an essential component of dynein mediated nuclear migration.

Using quantitative fluorescence techniques I was able to create a molecular inventory of …

Sex Difference In Calbindin Cell Number In The Mouse Preoptic Area: Effects Of Neonatal Estradiol And Bax Gene Deletion, Richard F. Gilmore Iii

Masters Theses 1911 - February 2014

The sexually dimorphic nucleus of the preoptic area (SDN-POA) was first discovered in rats and is one of the most famous and best studied sex differences in the field of neuroscience. Though well documented in rats (larger in males than females), this sex difference was only recently able to be observed in mice due to the discovery of the protein calbindin-D28k as a marker. Recent studies have shown a larger, more distinct calbindin-immunoreactive (ir) cell cluster in male mice compared to females. However, the exact location of the cluster and whether the sex difference is one of total cell number …

Pharmacological Chaperoning In Fabry Disease, Jerome Rogich

Masters Theses 1911 - February 2014

Fabry Disease is an X-­‐linked lysosomal storage disorder characterized by a variety of symptoms including hypohydrosis, seizures, cardiac abnormalities, skin lesions, and chronic pain. These symptoms stem from a lack of functional endogenous α-­‐ Galactosidase A (α-­GAL), which leads to an accrual of its natural substrate. The severity of the disease symptoms can be directly correlated with the amount of residual enzyme activity. It has been shown that an imino sugar, 1-deoxygalactonojirimycin (DGJ), can increase enzymatic activity and clear excess substrate. This pH-­‐dependent chaperoning phenomenon is believed to arise from the presence of aspartic acid 170 in the active site. …

Novel Adaptor-Dependent Domains Promote Processive Degradation By Clpxp, Keith L. Rood

Masters Theses 1911 - February 2014

Protein degradation by ATP dependent proteases is a universally conserved process. Recognition of substrates by such proteases commonly occurs via direct interaction or with the aid of a regulatory adaptor protein. An example of this regulation is found in Caulobacter crescentus, where key regulatory proteins are proteolysed in a cell-cycle dependent fashion. Substrates include essential transcription factors, structural proteins, and second messenger metabolism components. In this study, we explore sequence and structural requirements for regulated adaptor mediated degradation of PdeA, an important regulator of cyclic-di-GMP levels.

Robust degradation of PdeA is dependent on the response regulator CpdR in vivo …

In Vivo Investigations Of Polymer Conjugates As Therapeutics, Elizabeth M. Henchey

Masters Theses 1911 - February 2014

Polymer conjugates offer a way to introduce materials into the body that would normally be rejected or cause toxicity. Two polymers are investigated in vivo for uses in chemotherapeutic delivery, protein therapeutics, and DNA transfection. A novel polymer, polyMPC, has the ability to increase doxorubicin loading and its solubility, and is conjugated in a way to release its payload in a low pH environment. Through its conjugation, blood clearance time of doxorubicin is increased, and thus tumor exposure to the drug is increased with a single administration. It can be administered at ten times the concentration of free doxorubicin, and …