Shikha Dagar

Bio: Shikha Dagar is an academic researcher from Indian Institute of Science Education and Research, Pune. The author has contributed to research in topics: Chemistry & Membrane. The author has an hindex of 3, co-authored 5 publications receiving 22 citations. Previous affiliations of Shikha Dagar include Indian Institute of Science.

Prebiological Membranes and Their Role in the Emergence of Early Cellular Life.

Abstract: Membrane compartmentalization is a fundamental feature of contemporary cellular life. Given this, it is rational to assume that at some stage in the early origins of life, membrane compartments would have potentially emerged to form a dynamic semipermeable barrier in primitive cells (protocells), protecting them from their surrounding environment. It is thought that such prebiological membranes would likely have played a crucial role in the emergence and evolution of life on the early Earth. Extant biological membranes are highly organized and complex, which is a consequence of a protracted evolutionary history. On the other hand, prebiotic membrane assemblies, which are thought to have preceded sophisticated contemporary membranes, are hypothesized to have been relatively simple and composed of single chain amphiphiles. Recent studies indicate that the evolution of prebiotic membranes potentially resulted from interactions between the membrane and its physicochemical environment. These studies have also speculated on the origin, composition, function and influence of environmental conditions on protocellular membranes as the niche parameters would have directly influenced their composition and biophysical properties. Nonetheless, the evolutionary pathways involved in the transition from prebiological membranes to contemporary membranes are largely unknown. This review critically evaluates existing research on prebiotic membranes in terms of their probable origin, composition, energetics, function and evolution. Notably, we outline new approaches that can further our understanding about how prebiotic membranes might have evolved in response to relevant physicochemical parameters that would have acted as pertinent selection pressures on the early Earth.

Compositional heterogeneity confers selective advantage to model protocellular membranes during the origins of cellular life.

Abstract: Protocellular membranes are thought to be composed of mixtures of single chain amphiphiles, such as fatty acids and their derivatives, moieties that would have been part of the complex prebiotic chemical landscape. The composition and physico-chemical properties of these prebiological membranes would have been significantly affected and regulated by their environment. In this study, pertinent properties were systematically characterized, under early Earth conditions. Two different fatty acids were mixed with their respective alcohol and/or glycerol monoester derivatives to generate combinations of binary and tertiary membrane systems. Their properties were then evaluated as a function of multiple factors including their stability under varying pH, varying Mg2+ ion concentrations, dilution regimes, and their permeability to calcein. Our results demonstrate how environmental constraints would have acted as important prebiotic selection pressures to shape the evolution of prebiological membranes. The study also illustrates that compositionally diverse membrane systems are more stable and robust to multiple selection pressures, thereby making them more suitable for supporting protocellular life.

Geochemical influences on nonenzymatic oligomerization of prebiotically relevant cyclic nucleotides

Abstract: The spontaneous emergence of long RNA molecules on the early Earth, a phenomenon central to the RNA World hypothesis, continues to remain an enigma in the field of origins of life. Few studies have looked at the nonenzymatic oligomerization of cyclic mononucleotides under neutral to alkaline conditions, albeit in fully dehydrated state. In this study, we systematically investigated the oligomerization of cyclic nucleotides under prebiotically relevant conditions, wherein starting reactants were subjected to repeated dehydration-rehydration (DH-RH) regimes. DH-RH conditions, a recurring geological theme that was prevalent on prebiotic Earth, are driven by naturally occurring processes including diurnal cycles and tidal pool activity. These conditions have been shown to facilitate uphill oligomerization reactions. The polymerization of 2'-3' and 3'-5' cyclic nucleotides of a purine (adenosine) and a pyrimidine (cytidine) was investigated. Additionally, the effect of amphiphiles was also evaluated. Furthermore, to discern the effect of "realistic" conditions on this process, the reactions were also performed using a hot spring water sample from a candidate early Earth environment. Our study showed that the oligomerization of cyclic nucleotides under DH-RH conditions resulted in intact informational oligomers. Amphiphiles increased the stability of both the starting monomers and the resultant oligomers in selected reactions. In the hot spring reactions, both the oligomerization of nucleotides and the back hydrolysis of the resultant oligomers were pronounced. Altogether, this study demonstrates how nonenzymatic oligomerization of cyclic nucleotides, under both laboratory-simulated prebiotic conditions and in a candidate early Earth environment, could have resulted in RNA oligomers of a putative RNA World.

Porphyrin in Prebiotic Catalysis: Ascertaining a Route for the Emergence of Early Metalloporphyrins **

Abstract: Metal ions are known to catalyze certain prebiotic reactions. However, the transition from metal ions to extant metalloenzymes remains unclear. Porphyrins are found ubiquitously in the catalytic core of many ancient metalloenzymes. In this study, we evaluated the influence of porphyrin‐based organic scaffold, on the catalysis, emergence and putative molecular evolution of prebiotic metalloporphyrins. We studied the effect of porphyrins on the transition metal ion‐mediated oxidation of hydroquinone (HQ). We report a change in the catalytic activity of the metal ions in the presence of porphyrin. This was observed to be facilitated by the coordination between metal ions and porphyrins or by the formation of non‐coordinated complexes. The metal‐porphyrin complexes also oxidized NADH, underscoring its versatility at oxidizing more than one substrate. Our study highlights the selective advantage that some of the metal ions would have had in the presence of porphyrin, underscoring their role in shaping the evolution of protometalloenzymes.

Prebiological Membranes and Their Role in the Emergence of Early Cellular Life.

Abstract: Membrane compartmentalization is a fundamental feature of contemporary cellular life. Given this, it is rational to assume that at some stage in the early origins of life, membrane compartments would have potentially emerged to form a dynamic semipermeable barrier in primitive cells (protocells), protecting them from their surrounding environment. It is thought that such prebiological membranes would likely have played a crucial role in the emergence and evolution of life on the early Earth. Extant biological membranes are highly organized and complex, which is a consequence of a protracted evolutionary history. On the other hand, prebiotic membrane assemblies, which are thought to have preceded sophisticated contemporary membranes, are hypothesized to have been relatively simple and composed of single chain amphiphiles. Recent studies indicate that the evolution of prebiotic membranes potentially resulted from interactions between the membrane and its physicochemical environment. These studies have also speculated on the origin, composition, function and influence of environmental conditions on protocellular membranes as the niche parameters would have directly influenced their composition and biophysical properties. Nonetheless, the evolutionary pathways involved in the transition from prebiological membranes to contemporary membranes are largely unknown. This review critically evaluates existing research on prebiotic membranes in terms of their probable origin, composition, energetics, function and evolution. Notably, we outline new approaches that can further our understanding about how prebiotic membranes might have evolved in response to relevant physicochemical parameters that would have acted as pertinent selection pressures on the early Earth.

Author Correction: Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia.

Abstract: The original version of this Article contained an error in Figure 4. In panel i, the lower CYA and α-SMA images were inadvertently inverted. This has been corrected in both the PDF and HTML versions of the Article.

Phase Transition Induced Fission in Lipid Vesicles

Abstract: In this work we demonstrate how the first order phase transition in giant unilamellar vesicles (GUVs) can function as a trigger for membrane fission. When driven through their gel-fluid phase transition GUVs exhibit budding or pearl formation. These buds remain connected to the mother vesicle presumably by a small neck. Cooling these vesicles from the fluid phase (T>Tm) through the phase transition into the gel state (T

Correction: Fatty acids' double role in the prebiotic formation of a hydrophobic dipeptide

Abstract: Correction for ‘Fatty acids' double role in the prebiotic formation of a hydrophobic dipeptide’ by Sara Murillo-Sanchez et al., Chem. Sci., 2016, DOI: 10.1039/c5sc04796j.

Protocells: Milestones and Recent Advances.

Abstract: The origin of life is still one of humankind's great mysteries. At the transition between nonliving and living matter, protocells, initially featureless aggregates of abiotic matter, gain the structure and functions necessary to fulfill the criteria of life. Research addressing protocells as a central element in this transition is diverse and increasingly interdisciplinary. The authors review current protocell concepts and research directions, address milestones, challenges and existing hypotheses in the context of conditions on the early Earth, and provide a concise overview of current protocell research methods.