Biology subjects

Todorova, V.

Publications and source records attributed to Todorova, V..

5 recordsLinked to original sources

bioRxiv2026

Photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons

The retina metabolizes glucose into lactate, a hallmark of aerobic glycolysis known as the Warburg effect. Although evidence points to rod photoreceptors as the primary source of aerobic glycolysis, a comparison of the energy metabolism in different retinal neurons has yet to be performed. We combined two-photon fluorescence lifetime imaging of biosensors with pharmacological protocols to analyse metabolic dynamics in healthy and diseased photoreceptors and in inner retinal neurons. Our data reveal distinct metabolic profiles among retinal neurons, identify rods as the drivers of aerobic glycolysis, demonstrate that inner retinal neurons rely on oxidative phosphorylation, show that rods need both glycolysis and oxidative phosphorylation to maintain ATP levels, and suggest that rods can metabolize lactate. A mutation causing retinitis pigmentosa increases lactate production in rods but changes the energy metabolism only subtly otherwise. Our results improve the understanding of retinal physiology and are relevant for pathologies involving imbalanced energy metabolism.

neuroscience↗

bioRxiv2023

Global organelle profiling reveals subcellular localization and remodeling at proteome scale

Defining the subcellular distribution of all human proteins and its remodeling across cellular states remains a central goal in cell biology. Here, we present a high-resolution strategy to map subcellular organization using organelle immuno-capture coupled to mass spectrometry. We apply this proteomics workflow to a cell-wide collection of membranous and membrane-less compartments. A graph-based representation of our data reveals the subcellular localization of over 7,600 proteins, defines spatial protein networks, and uncovers interconnections between cellular compartments. We demonstrate that our approach can be deployed to comprehensively profile proteome remodeling during cellular perturbation. By characterizing the cellular landscape following hCoV-OC43 viral infection, we discover that many proteins are regulated by changes in their spatial distribution rather than by changes in their total abundance. Our results establish that proteome-wide analysis of subcellular remodeling provides essential insights for the elucidation of cellular responses. Our dataset can be explored at organelles.czbiohub.org.

cell biology↗

bioRxiv2023

The genetic architecture of the pepper metabolome provides insights into the regulation of capsianoside biosynthesis

Capsicum (pepper) is among the most economically important species worldwide, the fruit accumulates specialized metabolites with essential roles in plant environmental interaction and potential health benefits. However, the underlying genetic basis of their biosynthesis remains largely unknown. In this study, we developed and assessed both wild genetic variance and a bespoke mapping population to determine the genetic architecture of the pepper metabolome. The genetic analysis provided over 30 metabolic quantitative trait loci (mQTL) for over 1100 metabolites. We identified 92 candidate genes involved in various mQTL. Among the identified loci, we described and validated by transient overexpression a domestication gene cluster of eleven UDP-glycosyltransferases involved in monomeric capsianoside biosynthesis. We additionally constructed the biosynthetic reactions and annotated the genes involved in capsianoside biosynthesis in pepper. Given that differential glycosylation of acyclic diterpenoid glycosides contributes to plant resistance and acts as anticancer agents in humans, our data provide new insight, and resources for better understanding the biosynthesis of beneficial natural compounds to improve human health.

genetics↗

bioRxiv2023

An open-source FACS automation system for high-throughput cell biology

Recent advances in gene editing are enabling the engineering of cells with an unprecedented level of scale. To capitalize on this opportunity, new methods are needed to accelerate the different steps required to manufacture and handle engineered cells. Here, we describe the development of an integrated software and hardware platform to automate Fluorescence-Activated Cell Sorting (FACS), a central step for the selection of cells displaying desired molecular attributes. Sorting large numbers of samples is laborious, and, to date, no automated system exists to sequentially manage FACS samples, likely owing to the need to tailor sorting conditions ("gating") to each individual sample. Our platform is built around a commercial instrument and integrates the handling and transfer of samples to and from the instrument, autonomous control of the instruments software, and the algorithmic generation of sorting gates, resulting in walkaway functionality. Automation eliminates operator errors, standardizes gating conditions by eliminating operator-to-operator variations, and reduces hands-on labor by 93%. Moreover, our strategy for automating the operation of a commercial instrument control software in the absence of an Application Program Interface (API) exemplifies a universal solution for other instruments that lack an API. Our software and hardware designs are fully open-source and include step-by-step build documentation to contribute to a growing open ecosystem of tools for high-throughput cell biology.

bioengineering↗

bioRxiv2018

Levetiracetam and Rufinamide are effective at supressing spike and wave seizure activity in an in vitro model of absence epilepsy.

Spike-and-wave discharges (SpW) are seen in absence-type epilepsies. They are heterogeneous in terms of their clinical burden and their electrographic signature, which is used to classify different types of absence seizures; typical absence, in which SpW frequency is 3-4Hz and atypical absence, which shows a slower 1-2Hz frequency. Treatment of SpW varies dependent upon the syndrome, but both Valproic Acid (VPA) and Ethosuximide (ESM) are shown to be effective in controlling typical absence seizures. Other anti-epileptics (AEDs), Levetiracetam (LEV) and Rufinamide (RUF), have shown promise in treating absence epilepsies and their associated syndromes. Here we examine the efficacy of these AEDs on an in vitro model of SpW.\n\nBoth LEV and RUF show an effective reduction in both the number of SpW events and the spike component amplitude; VPA shows no effect, whilst ESM enhances the spike amplitude. Phenytoin exacerbates the SpW activity, increasing both the number of SpW, amplitude of the SpW and the number of spikes within each event. These data suggest that both LEV and RUF could be effective in the treatment of absence-type epilepsies. They also suggest this model could be an effective tool to test other AEDs aimed at treating atypical absence syndromes.

neuroscience↗