An Optical Technique for Mapping Microviscosity Dynamics in Cellular Organelles

Published date : 12 Apr 2018

Microscopic viscosity (microviscosity) is a key determinant of diffusion in the cell and defines the rate of biological processes occurring at the nanoscale, including enzyme-driven metabolism and protein folding. Here we establish a rotor-based organelle viscosity imaging (ROVI) methodology that enables real-time quantitative mapping of cell microviscosity. This approach uses environment-sensitive dyes termed molecular rotors, covalently linked to genetically encoded probes to provide compartment-specific microviscosity measurements via fluorescence lifetime imaging.

type
Journal Paper
journal
ACS Nano, 18 April 2018, doi: 10.1021/acsnano.8b00177
Impact Factor
13.942

Role of FcαR EC2 region in extracellular membrane localization

Published date : 05 Apr 2018

The FcαR receptor (CD89) binds to the constant region of Immunoglobulin (Ig) A to mediate mucosal immunity [1–2]. FcαR consist of five exons: two that code for the signal peptide regions S1 & S2, two for the extracellular regions EC1 and EC2, and the final exon for the transmembrane/cytoplasmic tail region [3]. Previously, we reported that the EC1 region plays an essential role for extracellular membrane localization of the receptor [4], where the absence of EC1 would prevent the variants from localizing to the cell surface, even with a full signal peptide.

type
Journal Paper
journal
Cell Cycle, 2018, doi: 10.1080/15384101.2018.1444236
Impact Factor
3.530

Effect of VH–VL Families in Pertuzumab and Trastuzumab Recombinant Production, Her2 and FcγIIA Binding

Published date : 14 Mar 2018

Many therapeutic antibodies are humanized from animal sources. In the humanization process, complementarity determining region grafting is tedious and highly prone to failure. With seven known VH families, and up to six known κ VL families, there are choices aplenty. However, the functions of these families remain largely enigmatic. To study the role of these V-region families, we made 84 recombinant combinations of the various VH and VL family whole IgG1 variants of both Trastuzumab and Pertuzumab.

type
Journal Paper
journal
Frontiers in Immunology, 12 March 2018, Vol. 9, Article: 469, doi: org/10.3389/fimmu.2018.00469
Impact Factor
6.429

The effect of molecular shape on oligomerization of hydrophobic drugs: molecular simulations of ciprofloxacin and Nutlin

Published date : 13 Mar 2018

Molecular aggregation plays a significant role in modulating the solubility, permeability, and bioactivity
of drugs. The propensity to aggregate depends on hydrophobicity and on molecular shape.
Molecular dynamics simulations coupled with enhanced sampling methods are used to explore the
early stages of oligomerization of two drug molecules which have a strong aggregation propensity, but
with contrasting molecule shapes: the antibiotic ciprofloxacin and the anticancer drug Nutlin-3A. The

type
Journal Paper
journal
The Journal of Chemical Physics 148, 104902 (2018); doi: 10.1063/1.5013056
Impact Factor
2.965

Structure-activity relationship studies of ultra-short peptides with potent activities against fluconazole-resistant Candida albicans

Published date : 09 Mar 2018

Vulvovaginal candidiasis (VVC) is a genital fungal infection afflicting approximately 75% of women globally and is primarily caused by the yeast Candida albicans. The extensive use of fluconazole, the first-line antifungal drug of choice, has led to the emergence of fluconazole-resistant C. albicans, creating a global clinical concern. This, coupled to the lack of new antifungal drugs entering the market over the past decade, has made it imperative for the introduction of new antifungal drug classes.

type
Journal Paper
journal
European Journal of Medicinal Chemistry, Vol. 150, 2018, Pg 479-490, doi: org/10.1016/j.ejmech.2018.03.027
Impact Factor
4.519

A computational model for how cells choose temporal or spatial sensing during chemotaxis

Published date : 05 Mar 2018

Cell size is thought to play an important role in choosing between temporal and spatial sensing in chemotaxis. Large cells are thought to use spatial sensing due to large chemical difference at its ends whereas small cells are incapable of spatial sensing due to rapid homogenization of proteins within the cell. However, small cells have been found to polarize and large cells like sperm cells undergo temporal sensing. Thus, it remains an open question what exactly governs spatial versus temporal sensing.

type
Journal Paper
journal
PLOS Computational Biology, 2018, 14(3), doi: 10.1371/journal.pcbi.1005966
Impact Factor
4.542

Molecular Insights into the Membrane Affinities of Model Hydrophobes

Published date : 01 Mar 2018

Membrane-active antibiotics are of great interest in fighting bacterial resistance. α-Mangostin is a membrane-active molecule, but there are no details of its mechanism of action at the atomistic level. We have employed free-energy simulations and microsecond-long conventional molecular dynamics simulations to study the mode of interaction of α-mangostin with a model bacterial membrane and compare it with the mechanisms of three hydrophobic molecules (ciprofloxacin, xanthone, and tetracycline).

type
Journal Paper
journal
ACS Omega 2018, 3, Pg. 2498-2507, doi: 10.1021/acsomega.7b01759

Active site CP-loop dynamics modulate substrate binding, catalysis, oligomerization, stability, over-oxidation and recycling of 2-Cys Peroxiredoxins

Published date : 21 Feb 2018

Peroxiredoxins (Prxs) catalyse the rapid reduction of hydrogen peroxide, organic hydroperoxide and peroxynitrite, using a fully conserved peroxidatic cysteine (CP) located in a conserved sequence Pxxx(T/S)xxCP motif known as CP-loop. In addition, Prxs are involved in cellular signaling pathways and regulate several redox-dependent process related disease. The effective catalysis of Prxs is associated with alterations in the CP-loop between reduced, Fully Folded (FF), and oxidized, Locally Unfolded (LU) conformations, which are linked to dramatic changes in the oligomeric structure.

type
Journal Paper
journal
Free Radical Biology and Medicine, Volume 118, April 2018, Pages 59-70, doi:10.1016/j.freeradbiomed.2018.02.027
Impact Factor
5.606