A5040351730- Protein Structure and Dynamics
- Heat shock proteins research
- RNA Research and Splicing
- Enzyme Structure and Function
- thermodynamics and calorimetric analyses
- Endoplasmic Reticulum Stress and Disease
- T-cell and B-cell Immunology
- Microbial Metabolic Engineering and Bioproduction
- Food composition and properties
- Molecular Junctions and Nanostructures
- Glycosylation and Glycoproteins Research
- Biochemical and Molecular Research
- Enzyme Production and Characterization
- Protein purification and stability
- RNA and protein synthesis mechanisms
- Advanced Fluorescence Microscopy Techniques
- Chemokine receptors and signaling
- Fungal and yeast genetics research
- Cancer Immunotherapy and Biomarkers
- MicroRNA in disease regulation
- Single-cell and spatial transcriptomics
- DNA and Nucleic Acid Chemistry
- Pneumocystis jirovecii pneumonia detection and treatment
- Photochemistry and Electron Transfer Studies
- RNA modifications and cancer
California University of Pennsylvania
2024
University of Pennsylvania
2023
University of Chicago
2016-2022
Temple University
2013
Heat shock induces a conserved transcriptional program regulated by heat factor 1 (Hsf1) in eukaryotic cells. Activation of this response is triggered heat-induced misfolding newly synthesized polypeptides, and so has been thought to depend on ongoing protein synthesis. Here, using the budding yeast Saccharomyces cerevisiae , we report discovery that Hsf1 can be robustly activated when synthesis inhibited, long as cells undergo cytosolic acidification. known cause transient intracellular...
Significance Oligomerization and glycosaminoglycan (GAG) binding are key regulatory steps for many extracellular ligands. Our analyses provide a structural basis of CC chemokine ligand 5 (CCL5) CCL3 oligomerization explain how affects the interaction these chemokines with GAG their functions. GAG-bound structures reveal CCL5 creates distinctive GAG-binding grooves to enhance via avidity regulating Furthermore, our structure may CXCL4, CXC chemokine, heterooligomerizes modulate...
In order to investigate experimentally observed phototautomerization of gas-phase cytosine, several excited-state tautomerization mechanisms were characterized at the EOM-CCSD and TDDFT levels. All pathways that took place exclusively on S1 surface found have significant barriers much higher than involved in radiationless decay cytosine tautomers through conical intersections back ground state; this fashion cannot compete with relaxation. However, an alternative possibility is facilitate...
Resistance to cancer therapy is driven by both cell-intrinsic and microenvironmental factors. Previous work has revealed that multiple resistant cell fates emerge in melanoma following treatment with targeted that,
Understanding how protein sequences confer function remains a defining challenge in molecular biology. Two approaches have yielded enormous insight yet are often pursued separately: structure-based, where sequence-encoded structures mediate function, and disorder-based, dictate physicochemical dynamical properties which determine the absence of stable structure. Here we study highly charged regions (>40% residues), routinely presumed to be disordered. Using recent advances structure...
The ability of Mycobacterium tuberculosis ( Mtb ) to persist in its host may enable an evolutionary advantage for drug resistant variants emerge. A potential strategy prevent persistence and gain efficacy is directly target the activity enzymes that are crucial persistence. We present a method expedited discovery structure-based design lead compounds by targeting hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical structural analyses AlaDH confirmed binding nucleoside...
Abstract Heat shock induces a conserved transcriptional program regulated by heat factor 1 (Hsf1) in eukaryotic cells. Activation of this heat-shock response is triggered heat-induced misfolding newly synthesized polypeptides, and so has been thought to depend on ongoing protein synthesis. Here, using the budding yeast Saccharomyces cerevisiae , we report discovery that Hsf1 can be robustly activated when synthesis inhibited, long as cells undergo cytosolic acidification. known cause...
The intracellular pH of yeast is a tightly regulated physiological cue that changes in response to growth state and environmental conditions.Fluorescent reporters, which have altered fluorescence local changes, can be used measure pH.While microscopy often make such measurements, it relatively low-throughput collecting enough data fully characterize populations cells challenging.Flow cytometry avoids this drawback, powerful tool allows for rapid, high-throughput measurement fluorescent...
Cellular stress induces rapid expression of genes encoding molecular chaperones. Stress also triggers transient intracellular acidification which, by unknown mechanisms, is broadly associated with increased resistance in eukaryotes. Here, using budding yeast as a model, we discover that preventing cells from transiently acidifying during heat shock compromises induction chaperones and fitness. Both subsequent restoration pH are required for robust chaperone induction, recovery production...
Understanding how protein sequences confer function remains a defining challenge in molecular biology. Two approaches have yielded enormous insight yet are often pursued separately: structure-based, where sequence-encoded structures mediate function, and disorder-based, dictate physicochemical dynamical properties which determine the absence of stable structure. Here we study highly charged regions (>40% residues), routinely presumed to be disordered. Using recent advances structure...
Single‐celled organisms must be able to dynamically respond changes in their environment ensure survival and replication. The budding yeast S. cerevisiae grows best acidic conditions, yet maintains cytosolic pH at or just above neutrality, expending a considerable portion of cellular ATP resources do so. When cells experience stresses such as high temperatures energy depletion, intracellular drops, equilibrating with the environment. Given strong buffering capacity cytosol, due mainly an...