Biology subjects

Kamal, M. M.

Publications and source records attributed to Kamal, M. M..

8 recordsLinked to original sources

bioRxiv2026

Cellular remodeling during photosymbiosis establishment revealed by single-cell dual proteomics

Endosymbiosis of phytoplankton in heterotrophic hosts is ecologically important and has led to key evolutionary innovations. However, the dynamic molecular processes underlying endosymbiosis establishment remain poorly understood. Here, using large-particle sorting and liquid chromatography-tandem mass spectrometry, we unravel heterogeneous changes in proteomes of the cosmopolitan ciliate Paramecium and algal endosymbiont Chlorella from engulfment to stable endosymbiosis. The initial digestion sees a sharp decline of intracellular Chlorella cells, along with host cellular reorganization involving a reduction of the cortex-localized defensive organelles, trichocysts, and proteins for intracellular transport and recycling. The remaining Chlorella cells enter a bottleneck stage characterized by energy production and cell cycle commitment before active proliferation. Comparison of Paramecium with successful and failed endosymbiosis further identifies a solute carrier transporter that potentially mediates metabolic homeostasis of the endosymbiotic system. Our study reveals inter-organismal coordination during the transition from predator-prey to host-endosymbiont relationships. The approach of time-course single-cell dual proteomics can be useful for investigating diverse interactions between microbial eukaryotes.

microbiology↗

bioRxiv2026

Endosymbiotic algal photosynthesis shapes diel transcriptome architecture in its ciliate host Paramecium bursaria

How photosynthetic endosymbionts reorganize host daily regulation remains unclear. Paramecium bursaria displays pronounced day-night behaviors, but whether its algal symbionts drive host temporal programs has been unresolved. We compared host gene expressions across a 24-hour light-dark cycle in symbiotic and aposymbiotic cells. Symbiotic cells exhibit an expanded and highly temporally ordered diel transcriptome compared with aposymbiotic cells. These rhythmic programs encompass motility, signaling, metabolism, and growth regulation, consistent with observed behaviors. Symbiosis-associated rhythmic programs recruit gene families encoding post-translational regulatory domains, including kinases, ubiquitin-related factors, WD40 scaffolds, and calcium-binding proteins, despite lacking recognizable canonical clock genes. Disrupting photosynthesis with paraquat altered these temporal profiles, shifting them toward an aposymbiotic-like state. A distantly related ciliate, Tetrahymena utriculariae, with an independently evolved symbiosis, showed similar symbiosis-associated daily programs, suggesting that photosynthetic endosymbionts can act as important organizers of host daily gene regulation in endosymbiotic protists.

evolutionary biology↗

bioRxiv2025

Host-derived lipid transfer and metabolic reprogramming in a ciliate-algal symbiosis

Symbiotic associations enable species to integrate complementary traits and adapt to novel environments. However, how the host and endosymbiont exchange nutrients remains poorly understood in most cases. Previously Paramecium bursaria cells were shown to reorganize lipid droplets to accommodate endosymbiotic Chlorella cells and interfering with lipid metabolism reduced the endosymbiont number. Here, we combined transcriptomics, lipidomics, imaging mass spectrometry, and stable-isotope tracing to investigate organic nutrient exchange in this symbiotic system. Our results reveal that endosymbiotic algae undergo extensive reprogramming of lipid metabolic pathways and accumulate markedly higher levels of triglycerides than free-living algae. Isotope-labeling experiments demonstrate that at least some of these lipids originate from the host, providing direct evidence for organic carbon transfer from Paramecium to its algal endosymbionts. Together, our results show that the establishment of symbiosis fundamentally reshapes algal lipid metabolism and uncover an unexpected host-to-symbiont lipid provisioning mechanism--opposite to the canonical direction of carbon flow observed in most photosynthetic symbioses. This work provides new insight into the metabolic principles that sustain and stabilize endosymbiotic partnerships.

microbiology↗

bioRxiv2025

Splicing regulation and intron evolution in the short-intron ciliate model of endosymbiosis Paramecium bursaria

The integration of symbionts into host cells during endosymbiosis significantly alters gene expression and cell physiology. Though alternative splicing facilitates cellular adaptation through rapid modulation of gene expression and protein isoform diversity, its regulatory role during endosymbiosis remains poorly understood. Paramecium bursaria, which harbors hundreds of Chlorella variabilis algae within its cytoplasm, offers a powerful model to study splicing during endosymbiosis, especially given its exceptionally short introns (median [~]24 nt). Using time-course RNA sequencing of symbiotic and aposymbiotic cells, we found that splicing, especially of 5 proximal introns, enhances gene expression. Moreover, we identified 883 genes with differentially spliced introns, particularly enriched in transmembrane transporters essential for establishing nutrient exchange between a host cell and algal symbionts. Splicing regulation correlated with expression changes in conserved spliceosome components, implicating that these factors act as splicing enhancers or repressors during symbiosis. By exploring intron orthology across ciliates, we found that conserved introns exhibited more efficient splicing, characterized by lower GC content and uniform length, suggesting that intron evolution favors features that optimize expression. Our study reveals how splicing contributes to host adaptation during endosymbiosis and highlights the evolutionary dynamics of short introns in eukaryotes. Key pointsParamecium retains conserved core spliceosome genes but employs unique splicing regulation. Alternative splicing regulates metabolism during endosymbiosis, especially for transporter genes. Older introns evolve toward [~]24 nt length and low GC for efficient splicing and expression.

evolutionary biology↗

bioRxiv2025

An early evolutionary stage of mutualistic endosymbiosis reveals a parasitic aspect of endosymbionts

Mutualistic endosymbiosis is a cornerstone of evolutionary innovation, enabling organisms to exploit diverse niches unavailable to individual species. However, our knowledge about the early evolutionary stage of this relationship remains limited. The association between the ciliate Tetrahymena utriculariae and its algal endosymbiont Micractinium tetrahymenae indicates an incipient stage of endosymbiosis. Although T. utriculariae cells rely on endosymbiotic algae to grow in low-oxygen conditions, they gradually lose the endosymbionts in aerobic conditions. Our comparative genomics reveals that the mitochondria-related genes of T. utriculariae are fast-evolving. Symbiotic cells display elongated mitochondria, which interact intimately with endosymbionts. Moreover, inhibiting mitochondrial fatty acid oxidation reduces host fitness but increases the endosymbiont population. Time-series transcriptomics reveal physiological fine-tuning of the host during day and night, underscoring adaptations for nutrient exchange and regulation. Notably, endosymbiotic algae downregulate photosynthesis-related genes compared with free-living cells, correlated with a substantially reduced chlorophyll content. These findings indicate that the endosymbionts exploit host metabolites to supplement reduced photosynthesis. Consistently, symbiotic Tetrahymena cells exhibit lower fitness under aerobic conditions than aposymbiotic cells. Our results support that mutualistic and parasitic relationships between symbiotic organisms are condition-dependent, especially at an early evolutionary stage.

evolutionary biology↗

bioRxiv2025

Spatial proteomics reveals lipid droplet reorganization in symbiotic Paramecium bursaria cells

Endosymbiosis is an important adaptive mechanism allowing organisms to exploit novel niches. The flexible relationship between the ciliate Paramecium bursaria and green algae represents a model system for studying early endosymbiosis evolution. However, the mechanisms underlying how P. bursaria cells maintain this endosymbiotic relationship remain unclear. Here, we use mass spectrometry-based proteomics to generate a spatial proteomic atlas of the host P. bursaria cells with and without endosymbionts. This atlas defines the protein composition of the endosymbiont-containing compartment (perialgal vacuole) and reveals pronounced remodeling of host lipid droplets upon symbiosis. Imaging analyses confirm that lipid droplets change in size, morphology, and positioning, accumulating near intracellular algae. Perturbing symbiotic cells with chemical inhibitors of lipid metabolism reduces endosymbiotic algal numbers, revealing a role for lipid droplets in the host-endosymbiont interaction. Our data provide a comprehensive resource for protein localization in P. bursaria cells and elucidate how those cells remodel an existing cellular compartment to maintain endosymbiosis.

biochemistry↗

bioRxiv2020

Behavioral, Biochemical and Histopathological effects of Standardised Pomegranate extract with Vinpocetine, Propolis or Cocoa in a rat model of Parkinsons disease

Introduction Parkinsonism is a neurodegenerative disorder. Pomegranate (POM) has been previously shown to have a dopaminergic neuroprotective effect against Parkinsonism.Objective The aim of the current study is to compare the efficacy of POM, vinpocetine, Propolis, Cocoa or L-dopa using RT-induced Parkinsonism rat model.Methods Rats were divided into seven groups; one normal and five RT model groups. One of the RT (2.5 mg/kg sc) groups served as non-treated parkinsonism model whereas the others were treated with either L-dopa (10 mg/kg PO) or with POM (150 mg/kg PO) together with each of the following; vinpocetine (VIN) (20 mg/kg PO), Propolis (300 mg/kg PO), Cocoa (24 mg/kg PO). Motor and cognitive performances were examined using three tests (catalepsy, open-field, Y-maze). Striatal dopamine, norepinephrine, serotonin, acetylcholinesterase, GABA, Glutamate, GSK 3B, BDNF levels were assessed as well as MDA, SOD, TAC, IL-1β, TNF-α, iNOs and caspase-3. Also, histopathological examinations of different brain regions were determined.Results Treatment with L-dopa alone or with all POM combination groups alleviated the deficits in locomotor activities, cognition, monoamine levels, acetylcholinesterase activity, oxidative stress, and inflammatory markers as well as caspase-3 expression induced by RT.Conclusion Combinations of POM with each of VIN, Propolis or Cocoa have a promising disease-modifying antiparkinsonian therapy even without being given as an adjuvant to L-dopa.View Full Text

animal behavior and cognition↗

bioRxiv2019

The mTORC1/S6K/PDCD4/eIF4A axis determines outcome of mitosis.

mTOR is a serine/threonine kinase which acts a master regulator of cell growth and proliferation. Raptor, a scaffolding protein that recruits substrates to mTOR complex 1 (mTORC1), is known to be phosphorylated during mitosis, but the significance of this phosphorylation remains largely unknown. Here we show that raptor expression and mTORC1 activity are dramatically reduced in mitotic arrested cells across a variety of cancer and normal cell lines. Prevention of raptor phosphorylation during mitosis resulted in reactivation of mTORC1 in a rapamycin-sensitive manner. Importantly, expression of a non-phosphorylatable raptor mutant caused a dramatic reduction in cytotoxicity of the spindle poison Taxol. This effect was mediated via degradation of Programmed Cell Death Protein 4 (PDCD4), a tumor suppressor protein that inhibits eIF4A activity and is negatively regulated by the mTORC1/S6K pathway. Moreover, pharmacological inhibition of eIF4A was able to enhance the effects of taxol and restore sensitivity in Taxol resistant cancer cells. These findings indicate that the mTORC1/S6K/PDCD4/eIF4A axis has a pivotal role in death vs. slippage decision during prolonged mitotic arrest and may be exploited to gain a clinical benefit in treating cancers resistant to anti-mitotic drugs.

molecular biology↗