A5087982660- Cancer therapeutics and mechanisms
- Plant Micronutrient Interactions and Effects
- Plant nutrient uptake and metabolism
- DNA and Nucleic Acid Chemistry
- Lung Cancer Research Studies
- DNA Repair Mechanisms
- Banana Cultivation and Research
- RNA and protein synthesis mechanisms
- Phytase and its Applications
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Plant Virus Research Studies
- Polyomavirus and related diseases
- Plant responses to water stress
- CRISPR and Genetic Engineering
- Membrane-based Ion Separation Techniques
- Ion channel regulation and function
- RNA Interference and Gene Delivery
- Synthesis and Biological Evaluation
- MicroRNA in disease regulation
- Trace Elements in Health
- Folate and B Vitamins Research
- Erythrocyte Function and Pathophysiology
- Bacteriophages and microbial interactions
- Microbial Metabolites in Food Biotechnology
Davidson College
2019-2023
Stephens College
2021
University of California, San Francisco
2016
University of California, Berkeley
2010-2014
QB3
2012-2014
Cold Spring Harbor Laboratory
2007
Howard Hughes Medical Institute
2007
Identifying the downstream targets of microRNAs (miRNAs) is essential to understanding cellular regulatory networks. We devised a direct biochemical method for miRNA target discovery that combined RNA-induced silencing complex (RISC) purification with microarray analysis bound mRNAs. Because miR-124a have been analyzed, we chose it as our model. honed approach both by examining determinants stable binding between RISC and synthetic RNAs in vitro determining dependency repression...
Type II topoisomerases are required for the management of DNA superhelicity and chromosome segregation, serve as frontline targets a variety small-molecule therapeutics. To better understand how these enzymes act in both contexts, we determined 2.9-Å-resolution structure cleavage core human topoisomerase IIα (TOP2A) bound to doubly nicked, 30-bp duplex oligonucleotide. In accord with prior biochemical structural studies, TOP2A significantly bends its substrate using bipartite, nucleolytic...
Significance The solute carrier (SLC) 4 transporters are membrane proteins that control bicarbonate transport in human red blood cells and regulate borate plants yeast. Previously, one member of the SLC4 family, Band 3, had its crystal structure determined, which showed it an outward-open state. We report here what is, to our knowledge, second protein, plant transporter Bor1. Critically, is occluded state open neither side membrane. Because a new state, we able compare model with other...
Proteins from thermophiles are generally more thermostable than their mesophilic homologs, but little is known about the evolutionary process driving these differences. Here we attempt to understand how diverse thermostabilities of bacterial ribonuclease H1 (RNH) proteins evolved. RNH Thermus thermophilus (ttRNH) and Escherichia coli (ecRNH) share similar structures differ in melting temperature (T(m)) by 20 °C. ttRNH's greater stability caused part presence residual structure unfolded...
Borate is an essential micronutrient in plants regulated by borate transporters, which also protect both yeast and from toxically high levels of share homology with the human SLC4 transporters. SLC4A11 linked to congenital hereditary endothelial dystrophy was initially reported transport before subsequent studies rebutted this conclusion. To better understand activities purported we tested ability eleven transporters A. thaliana O. sativa complement a BOR1 deletion S. cerevisiae . We show...
Borate transporters are membrane transport proteins that regulate intracellular borate levels. In plants, is a micronutrient essential for growth but toxic in excess, while yeast, unnecessary and export confers tolerance. share structural homology with human bicarbonate the SLC4 family despite low sequence identity differences transported solutes. Here, we characterize S. cerevisiae transporter Bor1p examine whether key biochemical features of extend to transporters. We show multiple...
The Solute Carrier 4 (SLC4) family of proteins is called the bicarbonate transporters and includes archetypal protein Anion Exchanger 1 (AE1, also known as Band 3), most abundant membrane in red blood cells. SLC4 homologous with borate transporters, which have been characterized plants fungi. It remains a significant technical challenge to express purify transport homogeneity quantities suitable for structural or functional studies. Here we describe detailed procedures overexpression...
In S. cerevisiae, borate resistance is mediated by the transport protein Bor1p. plants, role of more complicated given organism's need to prevent toxicity while maintaining high enough levels as a micronutrient that supports growth. As result these complex needs, transporter family has expanded in with seven transporters Arabidopsis thalianaand four Oryza sativa. humans, SLC4A11 been suggested borate, but this claim remains controversial. To better understand activities purported...
The Solute Carrier 4 (SLC4) family of proteins is called the bicarbonate transporters and includes archetypal protein Anion Exchanger 1 (AE1, also known as Band 3), most abundant membrane in red blood cells. SLC4 homologous with borate transporters, which have been characterized plants fungi. It remains a significant technical challenge to express purify transport homogeneity quantities suitable for structural or functional studies. Here we describe detailed procedures overexpression...
Borate transport proteins regulate the availability of borate, an essential plant micronutrient that is toxic in excess. transporters plants and fungi share sequence structural homology with SLC4 transporters, which suggests they might other key features. The archetypal member human Band 3, or Anion Exchanger 1 (AE1). AE1 most abundant membrane protein red blood cells where it exchanges bicarbonate chloride, mutations are linked to several diseases such as hereditary spherocytosis renal...
Many transporters and ion channels form higher-order structural complexes, but the functional significance of such protein complexes often remains unclear. Additionally, many recent studies have implicated lipid-binding as a key factor in formation multimeric membrane complexes. The SLC4 carry bicarbonate across membranes, are typified by Band 3, most abundant red blood cells. Structures multiple including 3 reveal homodimeric structures, role dimerization plays their function unknown. In...
The SLC4 family of transporters includes the archetypal transporter Band 3, or Anion Exchanger 1 (AE1), a bicarbonate and chloride ion exchanger essential for human respiration most abundant membrane protein in red blood cells. Mutations such as AE1 can lead to diseases hereditary spherocytosis renal tubular acidosis. shares sequence structural homology with borate transporters, which are found plants fungi regulate cellular levels protect against toxicity. Here we generated mutations S....