Biology subjects

Dogan, S.

Publications and source records attributed to Dogan, S..

5 recordsLinked to original sources

bioRxiv2026

Metabolic modeling links leaf anatomy to environment-specific benefits on the C3-C4 spectrum

C4 photosynthesis evolved from the ancestral C3 pathway through coordinated leaf anatomical and metabolic reorganization that concentrates CO2 to reduce photorespiration. Quantitative understanding of these structure-function relationships remains limited. Here we used anatomy-aware metabolic modeling of a mesophyll-bundle sheath cell system to analyze the interdependence between leaf anatomy and photosynthetic metabolism on the C3-C4 spectrum. Our model faithfully recapitulates the transitory steps from C3 to C4 photosynthesis, reveals a crucial role for plasmodesmata in enabling the C3 to C4 transition, and points at potential pre-C2 metabolic states that provide benefits under conditions that favor elevated photorespiration. Incorporating bundle cell suberisation with our model predicts reduction of PSII activity and dominance of the NADP-ME C4 subtype in leaves with suberized bundle sheath cells and proposes a role for oxygen evolution at PSII as a potential driver for this mechanism. Varying bundle sheath leakage and photorespiratory conditions along the C3-C4 spectrum identify conditions under which C3-C4 intermediate photosynthesis provides energetic benefits and underlines the notion of intermediate photosynthesis as a stable evolutionary state. Overall, our study sheds new light on the quantitative relationship between leaf anatomy and metabolism and its interaction with the environment and suggests targets for climate-adaptation in C3 plants.

plant biology↗

bioRxiv2022

Data-Driven Design of Protein-Derived Peptide Multiplexes for Biomimetic Detection of Exhaled Breath VOC Profiles

Exhaled human breath contains a rich mixture of volatile organic compounds (VOCs) whose concentration can vary in response to disease or other stressors. Using simulated odorant-binding proteins (OBPs) and machine learning methods, we designed a multiplex of short VOC- and carbon-binding peptide probes that detect the characteristic "VOC fingerprint". Specifically, we target VOCs associated with COVID-19 in a compact, molecular sensor array that directly transduces vapor composition into multi-channel electrical signals. Rapidly synthesizable, chimeric VOC- and solid-binding peptides were derived from selected OBPs using multi-sequence alignment with protein database structures. Selective peptide binding to targeted VOCs and sensor surfaces was validated using surface plasmon resonance spectroscopy and quartz crystal microbalance. VOC sensing was demonstrated by peptide-sensitized, exposed-channel carbon nanotube transistors. The data-to-device pipeline enables the development of novel devices for non-invasive monitoring, diagnostics of diseases, and environmental exposures assessment.

bioengineering↗

bioRxiv2020

Enhanced specificity of high sensitivity somatic variant profiling in cell-free DNA via paired normal sequencing: design, validation, and clinical experience of the MSK-ACCESS liquid biopsy assay

Circulating cell-free DNA (cfDNA) from blood plasma of cancer patients can be used to interrogate somatic tumor alterations non-invasively or when adequate tissue is unavailable. We have developed and clinically implemented MSK-ACCESS (Analysis of Circulating cfDNA to Evaluate Somatic Status), an NGS assay for detection of very low frequency somatic alterations in select exons and introns of 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 98% for a priori mutation profiling. To evaluate the performance and utility of MSK-ACCESS, we report results from the first 681 prospective blood samples (617 patients) that underwent clinical analysis to guide patient management. Somatic mutations, copy number, and/or structural variants were detected in 73% of the samples, and 56% of these circulating-tumor DNA (ctDNA) positive samples had clinically actionable alterations. The utilization of matched white blood cell sequencing allowed retention of somatic alterations while filtering out over 10,000 germline and clonal hematopoiesis variants, thereby greatly enhancing the specificity of the assay. Taken together, our experience illustrates the importance of analyzing a matched normal sample when interpreting cfDNA results and highlights the potential of cfDNA profiling to guide treatment selection, monitor treatment response, and identify mechanisms of treatment resistance.

genomics↗

bioRxiv2020

Activation of Macrophages by CpG DNA and LPS: an FTIR Spectroscopic Study

The innate immune response triggered by CpG DNA can improve host survival following pathogen challenge. Whether CpG ODN-mediated immune activation leads to global molecular changes in cells that are detectable by FTIR spectroscopy is currently unknown. Here, we used Attenuated Total Reflectance (ATR) Fourier Transform Infrared (FTIR) spectroscopy to monitor the molecular changes in murine macrophage RAW 264.7 cells upon activation with CpG DNA and lipopolysaccharide (LPS). By PCA analysis, we identified the sources of variation to follow with detailed spectral analysis. CpG DNA and LPS treatment increase the total nucleic acid concentration from the early periods post-activation, and DNA synthesis follows RNA synthesis. RNA-specific peak shows the activation state of macrophages in early periods post-treatment. CpG DNA and LPS result in an initial rapid increase in the total protein concentration, leveling off two hours post-activation. Both activated groups increase the concentration of fatty acids, triglycerides, and cholesterol, pointing out to a shared synthesis pathway and de novo lipogenesis. This study, for the first time, demonstrates the use of FTIR spectroscopy as an independent modality to monitor the activation dynamics of murine macrophages upon activation with CpG DNA and LPS.

biophysics↗

bioRxiv2020

Enzyme Kinetics and Inhibition parameters of Human Leukocyte Glucosylceramidase

Glucosylceramidase (GCase) is a lysosomal enzyme that catalyzes the cleavage of {beta}-glucosidic linkage of glucocerebroside (GC) into glucose and ceramide; thereby, plays an essential function in the degradation of complex lipids and the turnover of cellular membranes. The growing list of 460 mutations in the gene coding for it--glucosylceramidase beta acid 1 (GBA1)--is reported to abolish its catalytic activity and decrease its enzyme stability, associating it with severe health conditions such as Gaucher disease (GD), Parkinson Disease and Dementia with Lewy bodies. Although the three-dimensional structure of wild type glucosylceramidase is elucidated, little is known about its features in human cells. Moreover, alternative sources of GCase that prove to be effective in the treatment of diseases with enzyme treatment therapies, impose the need for simple and cost-effective procedures to study the enzyme behaviour. This work, for the first time, shows a well established, yet simple, cost- and time-efficient protocol for the study of GCase enzyme in human leukocytes by the artificial substrate PNPG. Characterization of the enzyme in human leukocytes for activation parameters (optimal pH, Km, and Vmax) and enzyme inhibition, was done. The results indicate that the optimum pH of GCase enzyme with PNPG is 5.1. The Km and Vmax values were 12.6mM and 333 U/mg, respectively. Gluconolactone successfully inhibits GCase in a competitive manner, with a Ki value of 0.023 mM and IC 50 of 0.047 mM. Glucose inhibition was uncompetitive with a Ki of 1.94 mM and IC50 of 55.3 mM. This is the first report for the inhibitory effect of glucose, {delta}-gluconolactone on leukocyte GCase activity.

biochemistry↗