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Biology subjects

Siddiqui, S. A.

Publications and source records attributed to Siddiqui, S. A..

4 recordsLinked to original sources

Algae bacteria associations provide metabolite-mediated protection against algicidal bacteria in a tripartite plankton community

Microalgal fitness in nature is shaped by interactions within a diverse microbial community, yet most experimental studies have examined algal-bacterial interactions in pairwise systems. It is well established that bacteria can exhibit growth promoting or inhibiting effects on co-existing algae. Comparatively little information is available about how additional partners can alter the outcome of diatom-bacteria interactions. In the present study, we screened the pairwise interaction of the marine diatom Skeletonema marinoi with ten different bacteria. This screening identified Marinobacter adhaerens as a growth promoting and Vibrio cyclitrophicus HSW24 as growth inhibiting partner. Growth inhibition of V. cyclitrophicus was associated with cell lysis, chain fragmentation and altered pigmentation whereas M. adhaerens supported increased chlorophyll a fluorescence, uniform pigmentation, intact chains and healthy cell morphology. In a tripartite community containing both bacteria and the alga, M. adhaerens protected S. marinoi from the inhibitory effect of V. cyclitrophicus in a density dependent manner. Comparative metabolomics revealed distinct metabolic profiles between the pairwise and tripartite interactions. This allowed to identify metabolites that were up-regulated in the tripartite community and therefore candidates for the observed protection. Among these, kynurenic acid and N-acetyltyramine were identified in bioassays as protective molecules, thus clearly highlighting the importance of secondary metabolites in this interaction. The present findings demonstrate that a third bacterial partner can alter the outcome of an antagonistic algal-bacterial interaction by means of chemical mediators. This work has implications for our understanding of microbial community functioning that cannot only be derived from the investigation of pairwise interactions.

microbiology↗

Branched and Linear F-actin Networks Control Directional Migration Switching Behavior on Aligned Collagen Fibrils

Directed cell migration is essential in many biological processes and is driven by a variety of directional cues, including aligned fibrils in the extracellular matrix (ECM), a phenomenon known as contact guidance. How different cells respond to aligned fibrils and how internal regulators like formins and Arp2/3 control contact guidance is unknown. In this study, a unique system to assemble aligned collagen fibrils on mica and to transfer them onto controllable substrates is used to probe contact guidance. This fibril alignment system reveals that cytoskeletal regulation through myosin contractility and not receptor expression drives contact guidance ability. Highly contractile cells exhibit high-fidelity contact guidance, weakly contractile cells ignore cues and moderately contractile cells use a mixture of both parallel and perpendicular migration strategies on aligned collagen fibrils. In addition to myosin contractility, formins and Arp2/3 control contact guidance in a reciprocal manner across a variety of cell types. Formins, mediators of linear F-actin structures, enhance contact guidance and Arp2/3, a mediator of branched F-actin structures, diminishes contact guidance. This controlled materials system reveals the importance of both myosin-mediated contractility as well as the antagonistic action of formins and Arp2/3 on contact guidance, providing potential targets to tune contact guidance.

bioengineering↗

Metabolic modeling of Hermetia illucens larvae resource allocation for high-value fatty acid production

All plant and animal kingdom organisms use highly connected biochemical networks to facilitate sustaining, proliferation and growth functions. While biochemical network details are well known, the understanding of intense regulation principles is still limited. We chose to investigate Hermetia illucens fly at the larval stage as it is crucial for successful resource accumulation and allocation for the consequential organisms developmental stages. We combined the iterative wet lab experiments and innovative metabolic modeling design approaches, to simulate and explain the H. illucens larval stage resource allocation processes and biotechnology potential. We performed time-based growth and high-value chemical compound accumulation wet lab chemical analysis experiments in larvae and Gainesville diet composition. To predict diet-based alterations on fatty acid allocation potential, we built and validated the first H. illucens medium-size stoichiometric metabolic model. Using optimization methods like Flux balance and Flux variability analysis on the novel insect metabolic model, it predicted that doubled essential amino acid consumption increased the growth rate by 32%, but pure glucose consumption had no positive impact on growth. In the case of doubled pure valine consumption, the model predicted a 2% higher growth rate. In this study, we describe a new framework to research the impact of dietary alterations on the metabolism of multi-cellular organisms at different developmental stages for improved, sustainable and directed high-value chemicals. Significance StatementMetabolic modeling serves as a platform for researchers to investigate and study in depth the possible states of the system based on the existing knowledgebase (e.g. metabolic reactions, substrates, products and their stoichiometry). These models can be applied for different industrial applications, to simulate resource allocation potential and growth conditions. Moreover, these models predict the required diet for living organisms and insects to improve survival and growth rates and accumulate higher-value products, like fatty acids.

systems biology↗

Unravelling Key Interactions and the Mechanism of Demethylation during hAGT mediated DNA Repair via Simulations

Alkylating agents possess the biggest threat to the genomic integrity of cell by damaging DNA bases through regular alkylation. Such damages are repaired by several automated machinery inside cell. O6-alkylguanine-DNA alkyltransferase (AGT) is such an enzyme which performs the direct repair of an alkylated guanine base by transferring the alkyl group to a Cysteine residue. In the present study using extensive MD simulations and hybrid QM/MM calculations, we have investigated the key interactions between the DNA lesion and the hAGT enzyme and elucidated the mechanisms of the demethylation of the guanine base. Our simulation shows that the DNA lesion is electrostatically stabilized by the enzyme and the Arg135 of hAGT enzyme provides the main driving force to flip the damaged base into the enzyme. The QM/MM calculations show demethylation of damaged base as a three step in thermodynamically feasible and irreversible manner. Our calculations show that the final products forms via Tyr114 in a facile way in contrast to the previously proposed Lys-mediated route.

biochemistry↗