# positions[].organizations[].parent[].label
Texas A&M University Naresh K. Vashisht College of Medicine

# overview
The primary focus of my laboratory is to decipher how proteins partition into different sub-compartments of the cell. Cellular membranes serve to compartmentalize biochemical reactions to specific microenvironments. Proteins cross these membranes via a diverse array of protein translocation systems, or translocons. My laboratory has investigated the detailed molecular function of three different protein transport machineries, the human nuclear pore complex (NPC) and the bacterial Sec and Tat general secretion machineries. We are a biophysics lab and our primary tools for deciphering molecular mechanisms and dynamics are super-resolution imaging and single molecule particle tracking approaches. Our aim is to develop detailed, molecular-scale, mechanistic models of protein transport processes. We recently demonstrated 3D imaging of cargo transport through nuclear pores on the millisecond timescale with 5-15 nm precision in all three dimensions. This will be a major tool going forward for multiple projects.

In 2018, we began a new project on membrane-less organelles, which are micrometer-scale cellular structures known as biomolecular condensates (BMCs) that contain high concentrations of intrinsically disordered proteins and RNA. These BMCs are generally agreed to arise from liquid-liquid phase separation (LLPS), which is the spontaneous partitioning into dense and dilute phases due to favorable interactions between the separating molecules. The high density of aggregation prone proteins in BMCs is thought to lead to the cellular inclusions found in patients with multiple neurological diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's and Alzheimer's diseases. We are using super-resolution and single molecule methods to probe the structural and dynamic heterogeneity of condensates formed from the fused in sarcoma (FUS) protein to identify the conditions that lead to solidification of liquid condensates (phase maturation).

# keywords[]
5102 Atomic, Molecular And Optical Physics

# keywords[]
1.1 Normal Biological Development And Functioning

# keywords[]
1.1 Normal Biological Development And Functioning

# keywords[]
1.1 Normal Biological Development And Functioning

# keywords[]
1.1 Normal Biological Development And Functioning

# educationAndTraining[].organization.label
California Institute of Technology - (Pasadena, California, United States)

# educationAndTraining[].organization.label
University of California, Berkeley - (Berkeley, California, United States)

# educationAndTraining[].organization.label
University of California, Davis - (Davis, California, United States)

# educationAndTraining[].organization.label
Brandeis University - (Waltham, Massachusetts, United States)

# awardsAndHonors[].label
Junior Faculty Research Excellence Award

# publications[].label
Single-molecule measurements of importin alpha/cargo complex dissociation at the nuclear pore.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Single giant vesicle rupture events reveal multiple mechanisms of glass-supported bilayer formation.

# publications[].label
Effect of average phospholipid curvature on supported bilayer formation on glass by vesicle fusion.

# publications[].label
Oligomerization state of the functional bacterial twin arginine translocation (Tat) receptor complex

# publications[].label
Tuning axial and lateral localization precision in 3D super-resolution microscopy with variable astigmatism.

# publications[].label
A Hinged Signal Peptide Hairpin Enables Tat-Dependent Protein Translocation.

# publications[].label
A series of spontaneously blinking dyes for super-resolution microscopy.

# publications[].label
High Throughput Screen for Escherichia coli Twin Arginine Translocation (Tat) Inhibitors.

# publications[].label
Kinetics of precursor interactions with the bacterial Tat translocase detected by real-time FRET.

# publications[].label
Position-dependent effects of polylysine on Sec protein transport.

# publications[].label
The Tat protein transport system: intriguing questions and conundrums.

# publications[].label
Detection of two histidyl ligands to CuA of cytochrome oxidase by 35-GHz ENDOR. 14,15N and 63,65Cu ENDOR studies of the CuA site in bovine heart cytochrome aa3 and cytochromes caa3 and ba3 from Thermus thermophilus

# publications[].label
FURTHER COMPARISON OF UBIQUINOL AND CYTOCHROME-C TERMINAL OXIDASES (VOL 335, PG 296, 1993)

# publications[].label
Could CuB be the site of redox linkage in cytochrome c oxidase?

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Spectroscopic characterization of heme A reconstituted myoglobin.

# publications[].label
Fluorescence quenching of reconstituted NCD-4-labeled cytochrome c oxidase complex by DOXYL-stearic acids.

# publications[].label
Comparison of ubiquinol and cytochrome c terminal oxidases. An alternative view.

# publications[].label
Cytochrome c oxidase: chemistry of a molecular machine.

# publications[].label
Further comparison of ubiquinol and cytochrome c terminal oxidases.

# publications[].label
Uncompetitive substrate inhibition and noncompetitive inhibition by 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT) and 2-n-nonyl-4-hydroxyquinoline-N-oxide (NQNO) is observed for the cytochrome bo3 complex: implications for a Q(H2)-loop proton translocation mechanism.

# publications[].label
Understanding the cytochrome c oxidase proton pump: thermodynamics of redox linkage.

# publications[].label
Deciphering the Structure and Function of Nuclear Pores Using Single-Molecule Fluorescence Approaches.

# publications[].label
Overlapping nuclear import and export paths unveiled by two-colour MINFLUX.

# publications[].label
Oligomerization state of the functional bacterial twin-arginine translocation (Tat) receptor complex.

# publications[].label
Further comparison of ubiquinol and cytochrome c terminal oxidases

# publications[].label
Investigating molecular crowding within nuclear pores using polarization-PALM.

# publications[].label
Effect of cargo size and shape on the transport efficiency of the bacterial Tat translocase.

# publications[].label
Choreography of importin-/CAS complex assembly and disassembly at nuclear pores.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Large cargo transport by nuclear pores: implications for the spatial organization of FG-nucleoporins.

# publications[].label
Two electrical potential-dependent steps are required for transport by the Escherichia coli Tat machinery.

# publications[].label
Interconvertibility of lipid- and translocon-bound forms of the bacterial Tat precursor pre-SufI.

# publications[].label
Bacterial Sec protein transport is rate-limited by precursor length: a single turnover study.

# publications[].publisher
American Society for Cell Biology (ASCB)

# publications[].label
Evolution of the cytochrome c oxidase proton pump.

# publications[].label
Super-resolved 3D Tracking of Cargo Transport Through Nuclear Pore Complexes by Astigmatism Imaging

# publications[].label
Proton transfer limits protein translocation rate by the thylakoid DeltapH/Tat machinery.

# publications[].label
Characterization of the early steps of OE17 precursor transport by the thylakoid DeltapH/Tat machinery.

# publications[].label
Influence of the TorD signal peptide chaperone on Tat-dependent protein translocation.

# publications[].label
Super-resolved 3D tracking of cargo transport through nuclear pore complexes.

# publications[].label
Influence of the TorD signal peptide chaperone on Tat-dependent protein translocation

# publications[].label
Single molecule studies of nucleocytoplasmic transport.

# publications[].label
Visualizing single molecules interacting with nuclear pore complexes by narrow-field epifluorescence microscopy.

# publications[].label
Nuclear import time and transport efficiency depend on importin beta concentration.

# publications[].label
Rapid Formation of a Semiquinone Species on Oxidation of Quinol by the Cytochrome bo3 Oxidase from Escherichia coli

# publications[].label
Imaging of single-molecule translocation through nuclear pore complexes.

# publications[].publisher
Proceedings of the National Academy of Sciences

# researcherOn[].label
Bacterial Export of Folded Proteins: Transport Mechanism of the Tat Translocon

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of General Medical Science

# researcherOn[].label
Mapping Transport Pathways Through Nuclear Pores Using 3D Super-Resolution Microscopy

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of General Medical Science

# streetAddress
Texas A&M Health Science Center; Cell Biology and Genetics; 1114 TAMU

# organizations[]
Texas A&M University Naresh K. Vashisht College of Medicine

# schools[]
Texas A&M University Naresh K. Vashisht College of Medicine

# etdChairOf[].label
Whitaker, Neal William 1982- (2012-12). Deciphering the Mechanism of E. coli tat Protein Transport: Kinetic Substeps and Cargo Properties. Doctoral Dissertation.