Biology subjects

Chakrabarti, L.

Publications and source records attributed to Chakrabarti, L..

9 recordsLinked to original sources

bioRxiv2026

Co-administration of simvastatin mitigates clozapine-induced lifespan extension and mitochondrial functional recovery in Drosophila melanogaster.

Antipsychotics and statins can be co-prescribed to combat the increased risk of high blood cholesterol with antipsychotic use. However, statins have been shown to interfere with mitochondrial functioning through reduced coenzyme Q expression, and second-generation antipsychotic, clozapine, has also demonstrated induced mitochondrial respiratory deficits in cell models. Despite this convergence, the combined effect of statins and antipsychotics on mitochondrial function, and mechanisms of overall health, remain poorly understood. Here we exploited the cholesterol auxotrophy of Drosophila melanogaster to investigate the effects of clozapine, simvastatin and their combination on lifespan and mitochondrial bioenergetics independently of cholesterol biosynthesis. Clozapine alone significantly extended median survival, an effect attenuated by simvastatin co-treatment. High resolution respirometry showed signs of clozapine-induced mitochondrial differences diminished with age, but this adaptation was also attenuated by simvastatin co-treatment. Using a spin probe (TEMPOL) with nitrogen-vacancy diamond quantum sensing, we directly measured free radical production and found that clozapine and simvastatin significantly increased free radical generation relative to the untreated control in early life stages. We also observed preliminary evidence of sex-specific differences in treatment response. Together, these findings suggest that clozapine induces an age-related mitochondrial adaptive response that is associated with extended lifespan and mitigated by simvastatin treatment.

physiology↗

bioRxiv2025

Detecting Mitochondrial Free Radicals with Quantum Sensors: From Organelles to a D. melanogaster Model of Neurodegeneration

This study identifies a distinct free radical signature in a D. melanogaster model of Parkinsons Disease, successfully differentiating Pink1-deficient flies from wild-type controls. This insight was achieved using a robust quantum sensing methodology for the selective detection of free radicals in biological systems. Our approach utilizes optically detected magnetic resonance (ODMR) and magnetic modulation (MM) protocols with nanodiamond nitrogen-vacancy (NV) centres. Selective identification is achieved using the spin probe TEMPOL, a cell-permeable superoxide dismutase 2 (SOD2) mimic that initially quenches the photoluminescence signal. Upon scavenging free radicals like hydroxyl and superoxide, TEMPOL is converted to a diamagnetic adduct, restoring the contrast and thus enabling quantitative detection. The approach was first validated in a chemical system with radical generation confirmed by electron paramagnetic resonance (EPR) spectroscopy. It was then demonstrated across biological scales, from isolated mitochondria and whole glioblastoma cells to the Drosophila model. In these studies, high-resolution respirometry revealed distinct free radical signatures, and findings were compared with NV T1 relaxometry. This work provides new biophysical insight into mitochondrial dysfunction, demonstrating a distinct free radical signature in a neurodegeneration model and connecting it to specific metabolic states.

cell biology↗

bioRxiv2023

Development of resident and migratory three-spined stickleback, Gasterosteus aculeatus.

The three-spined stickleback (Gasterosteus aculeatus) is a teleost fish and a model organism in evolutionary ecology, useful for both laboratory and natural experiments. It is especially valued for the substantial intraspecific variation in morphology, behaviour and genetics. Classic work of Swarup (1958) [1] has described the development in the laboratory of embryos from a single freshwater population, but this was carried out at higher temperature than many stickleback would encounter in the wild and variation between populations was not addressed. Here we describe the development of embryos from two sympatric, saltwater ecotypes of stickleback from North Uist, Scotland raised at 14{degrees}C, the approximate temperature of North Uist lochs in the breeding season. The two ecotypes were (a) a large, migratory form in which the adults are completely plated with bony armour and (b) a smaller, low-plated form that is resident year-round in saltwater lagoons. By monitoring embryos every 24-hours post fertilisation, important characteristics of development were observed and photographed to provide a reference for North Uist ecotypes at this temperature. Hatching success was greater than 85% and did not differ between resident and migratory stickleback, but migratory eggs hatched significantly earlier than the resident ecotype. Our work provides a framework that can now be used to compare stickleback populations that may also grow in distinct environmental conditions, to help understand the breadth of normal developmental features and to characterise abnormal development.

ecology↗

bioRxiv2022

A method to assess the mitochondrial respiratory capacity of complexes I and II from frozen tissue using the Oroboros O2k-FluoRespirometer

High-resolution respirometry methods allow for the assessment of oxygen consumption by the electron transfer systems within cells, tissue samples, and isolated mitochondrial preparations. As mitochondrial integrity is compromised by the process of cryopreservation, these methods have been limited to fresh samples. Here we present a simple method to assess the activity of mitochondria respiratory complexes I and II in previously cryopreserved murine skeletal muscle tissue homogenates, as well as previously frozen D. melanogaster, as a function of oxygen consumption.

cell biology↗

bioRxiv2021

B.1.1.7 and B.1.351 SARS-CoV-2 variants display enhanced Spike-mediated fusion

Severe COVID-19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS-CoV-2 spike protein expressed on the surface of infected cells interacts with the ACE2 receptor on neighbouring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha and Beta spread and fusion in cell cultures. Alpha and Beta replicated similarly to D614G reference strain in Vero, Caco-2, Calu-3 and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Alpha, Beta and D614G fusion was similarly inhibited by interferon induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes differentially modified fusogenicity, binding to ACE2 and recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS-CoV-2 emerging variants display enhanced syncytia formation. SynopsisThe Spike protein of the novel SARS-CoV-2 variants are comparative more fusogenic than the earlier strains. The mutations in the variant spike protein differential modulate syncytia formation, ACE2 binding, and antibody escape. O_LIThe spike protein of Alpha, Beta and Delta, in the absence of other viral proteins, induce more syncytia than D614G C_LIO_LIThe ACE2 affinity of the variant spike proteins correlates to their fusogenicity C_LIO_LIVariant associated mutations P681H, D1118H, and D215G augment cell-cell fusion, while antibody escape mutation E484K, K417N and {Delta}242-244 hamper it. C_LIO_LIVariant spike-mediated syncytia formation is effectively restricted by IFITMs C_LI

microbiology↗

bioRxiv2021

The elephant retina examined across a range of ages

The effect of aging in the human retina has been well documented, as have the signs of age-related retinal disease. Comparative studies in animals allow us to further investigate how the retina ages in different species. The African bush elephant (Loxodonta africana) has a retina comparable to other mammalian species, but with some reported distinctive differences in retinal ganglion cell (RGC) distribution and type. This is a first survey of the retina of Loxodonta africana from individuals aged 2 months to 32 years old. Gross examination, H&E staining and cell counts were used to compare calves (0-5 years), juveniles (6-10 years), sub-adults (11-20 years) and adults (>20 years). Dorsal-ventral eye diameter was shown to be significantly greater with age, whilst no significant changes in photoreceptor number were found. Changes in retinal thickness differed from past findings in elephants and humans, with thickness decreasing, then increasing in adults. Various morphological differences were evident in the samples including the presence of nuclei in the outer plexiform layer (OPL), degeneration of the inner plexiform layer (IPL), interruptions in nuclei columns of the outer nuclear layer (ONL), and larger unidentified cells within the inner nuclear layer (INL). These are initial observations provide some baseline information for a species where this range of samples has not been described previously.

zoology↗

bioRxiv2021

Sequence and structure comparison of ATP synthase F0 subunits 6 and 8 in notothenioid fish.

The Channichthyidae family (icefish) are the only known vertebrate species to be devoid of haemoglobin. Mitochondrial changes such as tight coupling of the mitochondria have facilitated sustained oxygen and respiratory activity in the fish. This makes it important to appreciate features in the sequence and structure of the proteins directly involved in proton transport, which could have physiological implications. ATP synthase subunit a (ATP6) and subunit 8 (ATP8) are proteins that function as part of the F0 component (proton pump) of the F0F1complex. Both are encoded by the mitochondrial genome and involved in oxidative phosphorylation. To explore mitochondrial sequence variation for ATP6 and ATP8 we have gathered sequences and predicted structures of these two proteins of fish from the Notothenioidei sub-order, a sub-Antarctic species. We compared these with seven other vertebrate species in order to reveal whether there might be physiologically important differences that can help us to understand the unique biology of the icefish.

evolutionary biology↗

bioRxiv2021

The dysregulated Pink1- Drosophila mitochondrial proteome is partially corrected with exercise.

One of the genes which has been linked to the onset of juvenile/early onset Parkinsons disease (PD) is PINK1. There is evidence that supports the therapeutic potential of exercise in the alleviation of PD symptoms. It is possible that exercise may enhance synaptic plasticity, protect against neuro-inflammation and modulate L-Dopa regulated signalling pathways. We explored the effects of exercise on Pink1 deficient Drosophila melanogaster which undergo neurodegeneration and muscle degeneration. We used a power-tower type exercise platform to deliver exercise activity to Pink1- and age matched wild-type flies. Mitochondrial proteomic profiles responding to exercise were obtained. Of the 516 proteins identified, 105 proteins had different levels between Pink1- and wild-type (WT) non-exercised D. melanogaster. Gene ontology enrichment analysis and STRING network analysis highlighted proteins and pathways with altered expression within the mitochondrial proteome. Comparison of the Pink1- exercised proteome to WT proteomes showed that exercising the Pink1- flies caused their proteomic profile to return towards wild-type levels.

cell biology↗

bioRxiv2020

The effect of E-liquid exposure on Caenorhabditis elegans.

E-cigarettes are being promoted as a less harmful alternative to smoking tobacco. However, vaping is a new phenomenon and safety profiles have not been fully established. Model organisms can be used to examine the cellular processes that may be changed by exposure to the E-liquids used for vaping. Mitochondria are essential in eukaryotic cells for production of ATP, protein biogenesis, metabolic pathways, cellular signalling, stress responses and apoptosis. Mitochondrial health can be used as a proxy for many aspects of healthy cellular physiology. Mutations in the PINK1 gene can lead to mitochondria-specific autophagy deficiency. We exposed two strains of Caenorhabditis elegans, CB5600 control and CC46 pink1, with 10% concentrations of nine different flavoured E liquids. We measured lifespan, movement, body size, brood size, and we examined their mitochondrial networks to investigate the effect of the E-liquids. We show that the CC46 (pink1) strain is affected by the E-liquids, even the flavours without nicotine, and that they have reduced lifespan, movement ability and mitochondrial organisation. We found that some E-liquids can dramatically shorten lifespan in this strain. Our data emphasise a need to carefully ascertain the potential harm that may be caused by the use of E-liquids.

cell biology↗