Biology subjects

Gandhi, H.

Publications and source records attributed to Gandhi, H..

10 recordsLinked to original sources

bioRxiv2026

Advancing Plant Health in Sub-Saharan Africa: Understanding National Agricultural Research Institutions capacities for Strategic Investment Priorities to Boost Genetic Gains Against Crop Biotic Stress

Plant health research within National Agricultural Research and Extension Systems (NARES) represents a critical yet neglected pillar of agricultural resilience in sub-Saharan Africa (SSA), where crop productivity remains substantially below global averages due to persistent biotic and abiotic stresses. Although plant health units have a strategic mandate to support crop protection, disease surveillance, and varietal improvement, the institutional capacity of these units across NARES in SSA is not defined. Here, we assessed 36 plant health units across 26 SSA countries to determine research capacity, identify operational constraints, and examine their contributions to crop improvement and food security. Our findings reveal the existence of a strong human capital operating under structurally constrained systems. More than 65% of personnel possess postgraduate qualifications, indicating the presence of a highly trained scientific workforce with considerable potential to drive plant health innovation. However, this expertise is undermined by severe infrastructural and institutional limitations that restrict research delivery. Access to essential facilities remains low, whereby only 53% of respondents had access to plant pathology laboratories, 43% had molecular biology platforms, and 37% had glass/screenhouses, while only 30% of respondents maintained phenotyping infrastructure such as sick plots or endemic/hot spot disease sites. These deficiencies undermine plant health research in areas like biotic stress resistance screening, pathogen diagnostics, and diversity. It was noted that plant health units primarily target staple food crops central to regional food systems, including cereals (maize, rice, sorghum, and millets), legumes (groundnut and cowpea), and root and tuber crops (cassava and potato). All these crops are affected by diverse biotic stresses that include fungi, bacteria, viruses, insect pests, and parasitic weeds. Yet research effectiveness to address these challenges is further constrained by unclear or fragmented protocols, poorly equipped laboratories, weak data capture, and management systems. Critical gaps were consistently identified in pathogen isolation and characterization, disease phenotyping, surveillance and mapping, experimental design, and data management. Workforce composition raises additional concerns regarding long-term system sustainability. Women account for only 18% of plant health personnel, while researchers younger than 35 years represent just 10% of the workforce, reflecting weak generational succession and gender inequity. These demographic imbalances constitute an existential threat to institutional continuity and innovation capacity. In summary, closing these gaps will require coordinated investment in infrastructure, technical training, institutional strengthening, and digital modernization. Equally important is the development of inclusive workforce strategies that improve gender representation and strengthen succession pathways. Unlocking the potential of NARES plant health networks is essential for accelerating resilient crop development, strengthening agricultural productivity, and advancing food security across SSA.

pathology↗

bioRxiv2025

Early-stage sparse testing strategies to increase genetic gain in plant breeding programmes

Early-stage sparse testing can significantly increase genetic gain in plant breeding programmes, facilitating the development of varieties with high and stable performance across farmers fields. This is achieved through (1) increased selection accuracy, enabled by broader sampling of trial sites across the Target Population of Environments (TPE), and (2) increased selection intensity by testing more selection candidates at a reduced replication rate. Early-stage agronomic testing typically involves evaluating a large number of selection candidates at one or a few experimental sites. Although these sites may poorly represent the TPE, strong selection pressure is generally applied. However, if the genetic correlation between performance at the experimental sites and in the TPE is low, most of the genetic gain achieved through selection will not be expressed under farmers conditions. Sparse testing addresses this challenge by using farm-as-incomplete-block designs, in which different subsets of selection candidates are evaluated across sites. By leveraging a genomic relationship matrix (GRM) to connect genotypes across environments, sparse testing enables early-stage multi-environment trials with broader coverage of the TPE. Here, we used stochastic simulation to compare various partially replicated sparse testing strategies to three fully replicated conventional early-stage testing strategies, with and without GRM. All sparse testing strategies achieved substantially higher and more stable genetic gain than the conventional strategies. Our results show that sparse testing provides breeders with a powerful and flexible framework to rethink early-stage trials and design cost-effective, multi-location experiments that lay the foundation for increased genetic gains in farmers fields. Key messageEarly-stage sparse testing can significantly increase genetic gain by (1) improving selection accuracy through broader sampling of the Target Population of Environments (TPE), and (2) increasing selection intensity.

genetics↗

bioRxiv2022

DeepVariant calling provides insights into race diversity and its implication for sorghum breeding

Due to evolutionary divergence, sorghum race populations exhibit vast genetic and morphological variations. A k-mer-based sorghum race sequence comparison identified the conserved k-mers of all sorghum race accessions and the race-specific genetic signatures identified the gene variability in 10,321 genes (PAVs). To understand the sorghum race structure, diversity and domestication, deep learning-based variant calling approach was employed in a set of genotypic data derived from a diverse panel of 272 sorghum accessions. The data resulted in 1.7 million high-quality genome-wide SNPs and identified selective signature (both positive and negative) regions through a genome-wide scan with different (iHS and XP-EHH) statistical methods. We discovered 2,370 genes associated with selection signatures including 179 selective sweep regions distributed over 10 chromosomes. Localization of these regions undergoing selective pressure with previously reported QTLs and genes revealed that the signatures of selection could be related to the domestication of important agronomic traits such as biomass and plant height. The developed k-mer signatures will be useful in the future to identify the sorghum race and SNP markers assist in plant breeding programs.

plant biology↗

bioRxiv2022

Heterotypic Endosomal Interactions Drive Emergent Early Endosomal Maturations

Endosomal maturation is critical for robust and timely cargo transport to specific cellular compartments. The most prominent model of early endosomal maturation involves phosphoinositide-driven gain or loss of specific proteins on individual endosomes, emphasising an autonomous and stochastic description. However, limitations in fast, volumetric imaging long hindered direct whole-cell measurements of absolute numbers of maturation events. Here, we use lattice light-sheet imaging and bespoke automated analysis to track individual very early (APPL1-positive) and early (EEA1-positive) endosomes over the entire population, demonstrating that direct interendosomal contact drives maturation. Using fluorescence lifetime, we show that this interaction is underpinned by asymmetric EEA1 binding to very early and early endosomes through its N- and C-termini, respectively. In combination with agent-based simulation that confirms a trigger-and-convert model, our findings indicate that APPL1-to EEA1-positive maturation is driven not by autonomous events but by heterotypic EEA1-mediated interactions, providing a mechanism for temporal and population-level control of maturation.

biophysics↗

bioRxiv2021

MOV10 facilitates messenger RNA decay in an N6-methyladenosine (m6A) dependent manner to maintain the mouse embryonic stem cells state

N6-methyladenosine (m6A) is the most predominant internal mRNA modification in eukaryotes, recognised by its reader proteins (so-called m6A-readers) for regulating subsequent mRNA fates -- splicing, export, localisation, decay, stability, and translation -- to control several biological processes. Although a few m6A-readers have been identified, yet the list is incomplete. Here, we identify a new m6A-reader protein, Moloney leukaemia virus 10 homologue (MOV10), in the m6A pathway. MOV10 recognises m6A-containing mRNAs with a conserved GGm6ACU motif. Mechanistic studies uncover that MOV10 facilitates mRNA decay of its bound m6A-containing mRNAs in an m6A-dependent manner within the cytoplasmic processing bodies (P-bodies). Furthermore, MOV10 decays the Gsk-3{beta} mRNA through m6A that stabilises the {beta}-CATENIN expression of a WNT/{beta}-CATENIN signalling pathway to regulate downstream NANOG expression for maintaining the mouse embryonic stem cells (mESCs) state. Thus, our findings reveal how a newly identified m6A-reader, MOV10 mediates mRNA decay via m6A that impact embryonic stem cell biology.

biochemistry↗

bioRxiv2021

Sorghum pan-genome explores the functional utility to accelerate the genetic gain

Sorghum (Sorghum bicolor L.) is one of the most important food crops in the arid and rainfed production ecologies. It is a part of resilient farming and is projected as a smart crop to overcome the food and nutritional challenges in the developing world. The development and characterisation of the sorghum pan-genome will provide insight into genome diversity and functionality, supporting sorghum improvement. We built a sorghum pan-genome using reference genomes as well as 354 genetically diverse sorghum accessions belonging to different races. We explored the structural and functional characteristics of the pan-genome and explain its utility in supporting genetic gain. The newly-developed pan-genome has a total of 35,719 genes, a core genome of 16,821 genes and an average of 32,795 genes in each cultivar. The variable genes are enriched with environment responsive genes and classify the sorghum accessions according to their race. We show that 53% of genes display presence-absence variation, and some of these variable genes are predicted to be functionally associated with drought traits. Using more than two million SNPs from the pan-genome, association analysis identified 398 SNPs significantly associated with important agronomic traits, of which, 92 were in genes. Drought gene expression analysis identified 1,788 genes that are functionally linked to different conditions, of which 79 were absent from the reference genome assembly. This study provides comprehensive genomic diversity resources in sorghum which can be used in genome assisted crop improvement.

bioinformatics↗

bioRxiv2020

Combination of photoactivation with lattice light-sheet imaging allows visualizing complex dorsal ruffling dynamics

Membrane protrusions that occur on the dorsal surface of a cell are an excellent experimental system to study actin machinery at work in a living cell. Small GTPase Rac1 controls the membrane protrusions that form and encapsulate extracellular volumes to perform pinocytic or phagocytic functions. Here, capitalizing on rapid volumetric imaging capabilities of lattice light-sheet microscopy (LLSM), we describe optogenetic approaches using photoactivable Rac1 (PA-Rac1) for controlled ruffle generation. We demonstrate that PA-Rac1 activation needs to be continuous, suggesting a threshold local concentration for sustained actin polymerization leading to ruffling. We show that Rac1 activation leads to actin assembly at the dorsal surface of the cell membrane that result in sheet-like protrusion formation without any requirement of a template. Further, this approach can be used to study the complex morpho-dynamics of the protrusions or to investigate specific proteins that may be enriched in the ruffles. Deactivating PA-Rac1 leads to complex contractile processes resulting in formation of macropinosomes. Using multicolour imaging in combination with these approaches, we find that Myo1e specifically is enriched in the ruffles.

biophysics↗

bioRxiv2019

Geometric regulation of histone state directs melanoma reprogramming

Malignant melanoma displays a high degree of cellular plasticity during disease progression, making classification of the heterogeneous population and selection of an appropriate therapy challenging. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation events that underlie tumorigenicity and dissemination. Here we uncover a relationship between geometric features at perimeter regions of multicellular melanoma aggregates, and reprogramming to a stem cell-like melanoma initiating cell (MIC) through histone marks H3K4Me2 and H3K9Ac. Using an in vitro tumor microengineering approach, we find concurrent expression of molecular MIC markers and spatial enrichment of these histone modifications at perimeter features. Chromatin immunoprecipitation and sequencing analysis demonstrates broad regulation of genes associated with SOX-, ETS-, and USF-families. SOX10 and PRDM14, transcriptional regulators with a putative role in several cancers, overlap with H3K9Ac and show elevated expression in cells along regions of perimeter curvature. siRNA knockdown of the epigenetic modifier PRDM14 abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma tumors may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity.

cancer biology↗

bioRxiv2018

Single molecule localization microscopy with autonomous feedback loops for ultrahigh precision

Single-molecule localization microscopy (SMLM) promises to provide truly molecular scale images of biological specimens1-5. However, mechanical instabilities in the instrument, readout errors and sample drift constitute significant challenges and severely limit both the useable data acquisition length and the localization accuracy of single molecule emitters6. Here, we developed an actively stabilized total internal fluorescence (TIRF) microscope that performs 3D real-time drift corrections and achieves a stability of [≤]1 nm. Self-alignment of the emission light path and corrections of readout errors of the camera automate channel alignment and ensure localization precisions of 1-4 nm in DNA origami structures and cells for different labels. We used Feedback SMLM to measure the separation distance of signaling receptors and phosphatases in T cells. Thus, an improved SMLM enables direct distance measurements between molecules in intact cells on the scale between 1-20 nm, potentially replacing Forster resonance energy transfer (FRET) to quantify molecular interactions7. In summary, by overcoming the major bottlenecks in SMLM imaging, it is possible to generate molecular images with nanometer accuracy and conduct distance measurements on the biological relevant length scales.

biophysics↗

bioRxiv2018

Rapid Whole Cell Imaging Reveals An APPL1-Dynein Nexus That Regulates Stimulated EGFR Trafficking

Multicellular life processes such as proliferation and differentiation depend on cell surface signaling receptors that bind ligands generally referred to as growth factors. Recently, it has emerged that the endosomal system provides rich signal processing capabilities for responses elicited by these factors [1-3]. At the single cell level, endosomal trafficking becomes a critical component of signal processing, as exemplified by the epidermal growth factor (EGF) receptors of the receptor tyrosine kinase family. EGFRs, once activated by EGF, are robustly trafficked to the phosphatase-enriched peri-nuclear region (PNR), where they are dephosphorylated [4-8]. However, the details of the mechanisms regulating the movements of stimulated EGFR in time and space, i.e., towards the PNR, are not known. What endosomal regulators provide specificity to EGFR? Do modifications to the receptor upon stimulation regulate its trafficking? To understand the events leading to EGFR translocation, and especially the early endosomal dynamics that immediately follow EGFR internalization, requires the real-time, long-term, whole-cell imaging of multiple elements. Here, exploiting the advantages of lattice light-sheet microscopy [9], we show that the binding of EGF by its receptor, EGFR, triggers a transient calcium increase that peaks by 30 s, causing the desorption of APPL1 from pre-existing endosomes within one minute, the rebinding of liberated APPL1 to EGFR within three minutes, and the dynein-dependent translocation of APPL1-EGF-bearing endosomes to the PNR within five minutes. The novel, cell spanning, fast acting network that we reveal integrates a cascade of events dedicated to the cohort movement of activated EGFR receptors. Our findings support the intriguing proposal that certain endosomal pathways have shed some of the stochastic strategies of traditional trafficking, and have evolved behaviors whose predictability is better suited to signaling [10, 11]. Work presented here demonstrates that our whole cell imaging approach can be a powerful tool in revealing critical transient interactions in key cellular processes such as receptor trafficking.

cell biology↗