Biology subjects

Karunakaran, R.

Publications and source records attributed to Karunakaran, R..

3 recordsLinked to original sources

bioRxiv2026

Transcriptomics and mutational analysis to screen immunogenic neoantigen peptides and Patient stratification based on immune subtypes for TNBC

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype with limited therapeutic options. In this study, we performed an integrative analysis of TNBC genomics data, including gene expression, somatic mutations, copy number alterations, survival outcomes, immune profiling, and clustering, to identify potential neoantigens, patient populations suitable for vaccination, and biomarkers for evaluating vaccine efficacy. This Integrated analysis identified POSTN and CAP1 as tumor-specific antigens. Incorporation of TNBC-specific mutations into the screened wild-type antigens led to the identification of three neoantigenic peptides with high potential for vaccine development. Immune subtyping stratified TNBC patients into four distinct subtypes, among which IS1 and IS3 were characterized by poor immune infiltration, lower mutation burden, and unfavorable prognosis, whereas IS2 and IS4 exhibited enhanced immune activity and better clinical outcomes. A vaccine incorporating the identified neoantigen peptides may potentially remodel the immune landscape of immune-cold subtypes (IS1 and IS3), converting them into immune-enriched phenotypes through vaccine-induced immune stimulation. Furthermore, weighted gene co-expression network analysis identified ten immune-related biomarkers from the blue and gray modules that were significantly associated with improved survival in IS2 and IS4. Functional enrichment and protein-protein interaction analyses revealed that hub genes primarily involved in immunoglobulin kappa chains and cytokine/TNF signaling pathways may serve as valuable immune biomarkers for prognostic assessment and monitoring vaccine efficacy.

cancer biology↗

bioRxiv2025

A gut-brain axis for aversive interoception drives innate and anticipatory emesis in Drosophila.

Signals from the gut are increasingly recognized as modulators of brain function and behavior. However, the pathways through which the gut conveys adverse or unpleasant information to the brain are still not well understood. In this study, we identify an aversive gut-brain axis in Drosophila melanogaster that detects toxin-induced gut damage and triggers both innate and learned anticipatory emesis (vomiting). After toxin ingestion, reactive oxygen species are produced by midgut enterocytes and detected by the transient receptor potential channel TrpA1 on nearby enteroendocrine cells. This sensing stimulates the release of neuropeptides from enteroendocrine cells, likely representing the gastric malaise flies experience after eating. We show that these neuropeptides act on specific serotonergic and dopaminergic neurons in the brain. These neurons interact with each other and signal to the downstream memory-related mushroom bodies to promote emesis. This circuit not only drives an immediate emetic response but also represents a malaise-driven aversive signal. The signal manifests as the persistent activity of dopaminergic neurons, which reinforces aversive valence to odor cues in the mushroom bodies. Thus, the flies learn that a specific odor predicts the presence of a toxin in food and exhibit anticipatory emesis upon re-exposure to the same odor. Taken together, we have identified an interoceptive signaling pathway that may be conserved for detecting harmful gut conditions and for remembering how to avoid them. Our work offers a mechanistic framework for studying aversive gut-brain communication involved in feeding, metabolism, depression, brain injury, and neurodegenerative diseases.

neuroscience↗

bioRxiv2022

Control of N2 fixation and NH3 excretion in Azorhizobium caulinodans ORS571

Due to the costly energy demands of N2 fixation, diazotrophic bacteria have evolved complex regulatory networks that permit expression of the N2-fixing catalyst nitrogenase only under conditions of N starvation, whereas the same condition stimulates upregulation of high-affinity NH3 assimilation by glutamine synthetase (GS), preventing excess release of excess NH3 for plants. Diazotrophic bacteria can be engineered to excrete NH3 by interference with GS, however control is required to minimise growth penalties and prevent unintended provision of NH3 to non-target plants. Here, we attempted two strategies to control GS regulation and NH3 excretion in our model cereal symbiont Azorhizobium caulinodans AcLP, a derivative of ORS571. We first attempted to recapitulate previous work where mutation of both PII homologues glnB and glnK stimulated GS shutdown but found that one of these genes was essential for growth. Secondly, we expressed unidirectional adenylyltransferases (uATs) in a {Delta}glnE mutant of AcLP which permitted strong GS shutdown and excretion of NH3 derived from N2 fixation and completely alleviated negative feedback regulation on nitrogenase expression. We placed a uAT allele under control of the NifA-dependent promoter PnifH, permitting GS shutdown and NH3 excretion specifically under microaerobic conditions, the same cue that initiates N2 fixation, then deleted nifA and transferred a rhizopine-inducible nifAL94Q/D95Q-rpoN controller plasmid into this strain, permitting coupled rhizopine-dependent activation of N2 fixation with NH3 excretion. In future, this highly sophisticated and multi-layered control circuitry could be used to activate N2 fixation and NH3 excretion specifically by AcLP colonising transgenic rhizopine producing cereals, targeting delivery of fixed N to the crop, and preventing interaction with non-target plants. Author SummaryInoculation of cereal crops with associative "diazotrophic" bacteria that convert atmospheric N2 to NH3 could be used to sustainably improve delivery of nitrogen in agriculture. However, due to the costly energy demands of N2 fixation, natural diazotrophic bacteria have evolved to conserve energy by preventing excess production of NH3 and release to the plants. Diazotrophs can be engineered for excess NH3 production and release, however genetic control is required to minimise growth penalties and prevent unintended provision of NH3 to non-target weed species. Here, we engineer control of N2 fixation and NH3 excretion in response to the signalling molecule rhizopine which is produced by transgenic barley. This control could be used to establish plant host-specific activation of N2 fixation and NH3 release following root colonisation in the field, minimising bacterial energy requirements in the bulk soil and preventing provision of NH3 to non-target plants.

microbiology↗