Biology subjects

Ozturk, M. S.

Publications and source records attributed to Ozturk, M. S..

3 recordsLinked to original sources

bioRxiv2023

Thermogenetic control of Ca2+ levels in cells and tissues

Virtually all major processes in cells and tissues are regulated by calcium ions (Ca2+). Understanding the influence of Ca2+ on cell function requires technologies that allow for non-invasive manipulation of intracellular calcium levels including the formation of calcium patterns, ideally in a way that is expandable to intact organisms. The currently existing tools for optical and optogenetic Ca2+ manipulation are limited with respect to response time, and tissue penetration depth. Here we present Genetically Encoded Calcium Controller (GECCO), a system for thermogenetic Ca2+ manipulation based on snake TRP channels optically controlled by infrared illumination. GECCO is functional in animal and plant cells and allows studying how cells decode different profiles of Ca2+ signals. GECCO enabled the shaping of insulin release from {beta}-cells, the identification of drugs that potentiate Ca2+-induced insulin release, and the generation of synthetic Ca2+ signatures in plants.

synthetic biology↗

bioRxiv2020

In-vivo monitoring and quantification of breast cancer growth dynamics with non-invasive intravital mesoscopic fluorescence molecular tomography

Preclinical breast tumor models are an invaluable tool to systematically study tumor progression and treatment response, yet methods to non-invasively monitor the involved molecular and mechanistic properties under physiologically relevant conditions are limited. Here we present an intravital mesoscopic fluorescence molecular tomography (henceforth IFT) approach that is capable of tracking fluorescently labeled tumor cells in a quantitative manner inside the mammary gland of living mice. Our mesoscopic approach is entirely non-invasive and thus permits prolonged observational periods of several months. The relatively high sensitivity and spatial resolution further enable inferring the overall number of oncogene-expressing tumor cells as well as their tumor volume over the entire cycle from early tumor growth to residual disease following the treatment phase. We find that sheer tumor volume, as commonly assessed by other imaging modalities, is not well correlated to tumor cell quantity, hence our IFT approach is a promising new method for studying tumor growth dynamics in a quantitative and longitudinal fashion in-vivo.

bioengineering↗

bioRxiv2019

High-Resolution Tomographic Analysis of in vitro 3D Glioblastoma Tumor Model under Long-Term Drug Treatment

Glioblastoma multiforme (GBM) is an extremely lethal type of brain tumor as it frequently develops therapeutic resistance over months of chemotherapy cycles. Hence, there is a critical need to provide relevant biological systems to guide the development of new potent personalized drugs but also efficient methodologies that enable personalized prediction of various therapeutic regimens for enhanced patient prognosis. Towards this goal, we report on the development of i) an appropriate in vitro model that mimics the 3D tumor microenvironment and ii) a companion imaging modality that enables to assess this in vitro model in its entirety. More precisely, we developed an integrated platform of bio-printing in vitro 3D GBM models and mesoscopic imaging to monitor tumor growth and invasion along with long-term drug treatment. The newly-developed in vitro 3D model contains tumor spheroids made of patient-derived glioma stem cells with a fluorescent reporter and vascular channels for drug perfusion. The imaging of these thick tissue constructs was performed using our second-Generation Mesoscopic Fluorescence Molecular Tomography (2GMFMT) imaging system which delivered 3D reconstruction of the fluidic channels and the GBM spheroids over the course of pre- and post-drug treatment (up to 70 days). The 2D measurements collected via 2GMFMT was comparable to existing imaging modalities, but 2GMFMT enabled non-sacrificial volumetric monitoring that provided a unique insgiht into the GBM spheroid growth and drug response. Overall, our integrated platform provides customizable in vitro model systems combined with an efficient long-term non-sacrificial imaging for the volumetric change of tumor mass, thus has a great potential in profoundly affecting the drug pipeline for a vast array of pathologies as well as for guiding personalized therapeutic regimen.

bioengineering↗