IISER MOHALI

Research findings from the group of Prof. Mahak Sharma in collaboration with Prof. Rajesh Ramachandran and Dr. Tripta Bhatia

The neuropathy-linked protein TECPR2 is a Rab5 effector that regulates cargo recycling from early endosomes

This study, published in Nature Communications (2025) by Sankalita Paul et al., identifies the cellular function of TECPR2 (Tectonin-β-propeller repeat containing protein 2), a protein whose mutation is linked to a form of Hereditary Sensory and Autonomic Neuropathy (HSAN), a severe neurodegenerative disorder.

This work provides a mechanistic understanding of how TECPR2 regulates the formation of specialized membrane subdomains that govern the fate of critical receptors, offering vital insights into the molecular etiology of HSAN.

(DOI: https://doi.org/10.1038/s41467-025-65568-4)

Figure: Summary of TECPR2 functional analyses in zebrafish.

A Yeast two-hybrid interaction of zebrafish Tecpr2 and the R1234W mutant with Rab5.
B Developmental expression profile of tecpr2 mRNA.
C In situ hybridization showing spatial tecpr2 expression during embryogenesis.
D, E Dose-dependent effects of tecpr2 morpholino on embryo survival (24 hpf) and hatching (72 hpf), with rescue by WT but not R1234W mRNA.
F Morphological defects in tecpr2 morphants and partial rescue outcomes.
G Representative NMJ staining in control, tecpr2 morphants, and rescue conditions.
H, I Quantification of α-BTX and SV2 areas from NMJ imaging.

(Image Credits)

Fungus-farming termites can protect their crop by confining weeds with fungistatic soil boluses

This study, published in Science (2025) by Aanchal Panchal et al., reveals the sophisticated pest management strategy employed by fungus-farming termites (Odontotermes obesus) to protect their vital fungal crop. It shows that termites actively combat invasive fungal weeds (Pseudoxylaria) by encasing them in specialized soil boluses containing fungistatic microbes. This research highlights a novel, highly targeted defense mechanism where insects integrate specific behaviors with microbial allies to selectively suppress fungal invaders without damaging their cultivated food source, offering key insights into co-evolutionary relationships and potential avenues for natural product discovery.

(DOI: https://doi.org/10.1126/science.adr2713)

Figure: O. obesus behavior in response to introduced Pseudoxylaria tuft on comb.

(A) Experimental setup: 20 major workers in an arena with 20 g of autoclaved, moistened soil containing two pieces of fresh fungus combs (FC). FC (left) is the control and FC+P (right) is the fresh comb with an introduced tuft of Pseudoxylaria. (B) (Left) Representative pictures of the different behaviors shown by termites (movies S1 to S3). Yellow arrows indicate the removed Pseudoxylaria hyphae. The bar charts (middle) represent the percentage of plates with the corresponding behavioral outcomes. The darker portions in the pie charts (right) denote the efficiency (in percentage) of each behavior in controlling Pseudoxylaria. (C) Area of comb scraped by the workers on FC versus FC+P (Wilcoxon-signed rank test, P < 0.001). (D) Efficiency of termites in controlling Pseudoxylaria compared with controls lacking termites. Lowercase letters (a, b, c, and d) denote significant statistical differences in a two-proportion Z test (table S1A). (Image Credits: https://www.science.org/ )

Decoding Organic Matter Sources in Himalayan Lakes Using Molecular Markers

This study, published in Ecological Indicators (2025) by Sunil Kumar et al., provides critical insights into the environmental health and ecological dynamics of Northwest Himalayan lakes. The research used lipid biomarkers—molecular fossils like n-alkanes and highly branched isoprenoids (HBIs)—in lake sediments to determine the origins and preservation of organic matter (OM).

This comparative analysis of Manasbal, Renuka, and Ahansar lakes highlights the utility of lipid biomarkers in tracing OM sources, which is essential for developing effective strategies for protecting these vital freshwater ecosystems under increasing anthropogenic and environmental pressures.

(DOI: https://doi.org/10.1016/j.ecolind.2025.113701)

Figure: Location map and bathymetry of the study area (Image corresponds to May 2023; Source: Google Earth). The locations of Ahansar Lake (AR) and Renuka Lake (RNK) discussed in the text are also shown (Image Credits: https://www.sciencedirect.com/ )

This study, published in Nature Communications (2025) by Pritam Saha et al., explores how tiny changes (mutations) in the tip-link protein—essential for hearing—can lead to hearing loss. It reveals how prolonged force from loud sound affects the protein’s structure and function, highlighting key molecular interactions that influence its stability and behavior. By comparing normal and mutant proteins, the research sheds light on how hearing-related proteins have evolved to handle mechanical stress.

Figure: (a). Design of a Lab-built Magnetic Tweezer with single-biomolecule tether, (b). example of 5 minutes long force-clamp data with microstates, and (c,d,e,f) varying mechano-stability of wild-type variants and mutant, showing stochasticity in folding dynamics and (g) and quantitative estimation of cooperativity of the protein variants.

This image on the cover of the November issue of the Journal of Bacteriology prefaces a paper by Archit Gupta and Purnananda Guptasarma in the issue, showing that E. Coli cells advance into simulacrums of bacterial biofilms consisting of phase separated condensates of extracellular DNA, lipopolysaccharide and Nucleoid Associated Proteins such as the histone-like protein, HU. The work carries forward earlier discoveries published in two recent papers in the Journal of Biological Chemistry by the Guptasarma group showing that HU uses its DNA binding sites to bind to both extracellular DNA and sugar-phosphate moieties on lipopolysachharide, and also that HU phase separates with DNA in the bacterial chromosome and in the matrix of expelled extracellular DNA in biofilms..

Towards a healthy aging…….

The investigators discover Rab8a, a small GTPase, as a key molecular regulator whose deficiency results in impaired functions of dendritic cells (DCs) in an aging host. The Rab8a reconstituted aged DCs generate potent antiviral IFN response and efficiently expand virus-specific cytotoxic T cells to better control influenza A virus. Such an approach would be valuable for achieving a favourable outcome of infections in the aging populations.

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Selected as a quarterly HOT article collection in Dalton Transactions.

Dr. Kuduva R. Vignesh's paper was selected as a quarterly HOT article collection in Dalton Transactions. This paper presents theoretical research that revealed important aspects of the magnetic characteristics of {M3Ln3} (M = Ni(II), Cu(II), Zn(II) and Ln = Dy(III), Tb(III), Gd(III)) complexes, particularly the influence of different bridging ligands, including peroxide and hydroxide ions, on the Single-Molecule Magnetic (SMM) and Single-Molecule Toroic (SMT) properties. Detailed state-of-the-art ab initio and Density functional theory (DFT) calculations have been undertaken to understand these properties on nine of the fascinating {M3Ln3} double-triangular complexes that possess a peroxide ligand. The experimental magnetic relaxation process and the magnetic exchange interactions for all complexes were explained by the performed calculations, which also strongly imply that the peroxide bridge plays a role in observing SMM behavior in these systems. On the other hand, this peroxide bridge does not support the SMT behavior. Through model studies, it has been discovered that as compared to the LoProp charges of peroxide ion, the greater negative charges on the bridging hydroxide ion reduce quantum tunneling of magnetization (QTM) effects, enabling more desired SMM characteristics and also lead to good SMT behavior.

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Dalton Transactions post on X.