Biological and Life Sciences

Professor Manish Grover completed his PhD in 2014 at the Indian Institute of Science, Bengaluru, under the guidance of Professor Utpal Tatu, where he investigated multiple aspects of malaria pathogenesis. Using a combination of biochemical, cell biology, and proteomic approaches, he uncovered the role of exported heat shock proteins in host cell remodelling and the role of ER stress in gametocytogenesis. In 2015, driven by a keen desire to learn genetics and genomics, he moved to the École Normale Supérieure de Lyon in France for his postdoctoral research with Dr Hugo Aguilaniu. There, he explored how the interplay between steroid signalling and notch signalling pathways regulates development and ageing in the nematode Caenorhabditis elegans.

In early 2018, he moved to the UK to work with Dr Michalis Barkoulas at Imperial College London. Here, his research focused on innate immune signalling and inter-tissue communication, particularly in the context of pathogen recognition. This work led to the discovery of a new immune response pathway in C. elegans that integrates conserved and species-specific mechanisms to defend against oomycetes—a group of animal pathogens previously understudied due to the absence of a suitable model and often mistaken for fungi.

At Ahmedabad University, he will continue working with the nematode model system to broadly investigate the systemic regulation of responses to prolonged heat stress and emerging infections driven by climate change.

Professor Grover's research in the Barkoulas Lab (Imperial College London) focused on understanding how C. elegans detects and defends natural pathogens, particularly on understudied fungi-like pathogens known as oomycetes. The work revealed that C. elegans can specifically recognise oomycetes and initiate an anticipatory protective transcriptional programme characterised by the induction of multiple chitinase-like (chil) genes in the epidermis. These CHIL proteins help modify the worm's cuticle, reducing pathogen attachment and antagonising infection.

To further understand the mechanism of immune activation against oomycetes, genetic screens were performed and paired C-type lectin receptors were found to mediate oomycete recognition specifically. This recognition triggers a complex communication cascade from neurons and the intestine to the epidermis, where a kinase-pseudokinase pair activated immune-response genes. While all these players identified were nematode-specific, their expression was controlled by conserved homeodomain factors. Additionally, the signalling pathway mirrored HER2/HER3 signalling axis in cancer and the NF-κB pathway in mammals. These findings highlight an interplay of conserved and species-specific factors along with cross-tissue communication in coordinating immune responses throughout an entire organism.

At Ahmedabad University, Professor Grover will broadly focus on understanding the systemic regulation of responses to prolonged heat stress. Taking advantage of the genetic tractability and defined anatomy of C. elegans, he aims to dissect how different tissues sense, withstand, and communicate during chronic thermal stress, and how microbiome composition and genetic background shape these systemic adaptations. Additionally, he plans to explore the suitability of C. elegans as a model to study emerging infections associated with climate change while also continuing on the regulation of the above-described signalling pathway to antagonize oomycetes.

Following is the list of publications from Professor Grover’s postdoctoral research at Imperial College London. For complete list, visit Google Scholar page

• Liu, K., Grover, M., Trusch, F., Vagena-Pantoula, C., Ippolito, D., & Barkoulas, M. (2024). Paired C-type lectin receptors mediate specific recognition of divergent oomycete pathogens in C. elegans. Cell Reports, 43(11), 114906. https://doi.org/10.1016/j.celrep.2024.114906
• Grover, M., Gang, S. S., Troemel, E. R., & Barkoulas, M. (2024). Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans. PLoS Biology, 22(3), e3002543. https://doi.org/10.1371/journal.pbio.3002543
• Drury, F., Grover, M., Hintze, M., Saunders, J., Fasseas, M. K., Constantinou, C., & Barkoulas, M. (2023). A PAX6-regulated receptor tyrosine kinase pairs with a pseudokinase to activate immune defense upon oomycete recognition in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 120(39), e2300587120. https://doi.org/10.1073/pnas.2300587120
• Gang, S. S., Grover, M., Reddy, K. C., Raman, D., Chang, Y., Ekiert, D. C., Barkoulas, M., & Troemel, E. R. (2022). A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans. PLoS Genetics, 18(10), e1010314. https://doi.org/10.1371/journal.pgen.1010314
• Grover, M., Fasseas, M. K., Essmann, C., Liu, K., Braendle, C., Félix, M. A., Glockling, S. L., & Barkoulas, M. (2021). Infection of C. elegans by Haptoglossa Species Reveals Shared Features in the Host Response to Oomycete Detection. Frontiers in Cellular and Infection Microbiology, 11, 733094. https://doi.org/10.3389/fcimb.2021.733094
• Grover, M., & Barkoulas, M. (2021). C. elegans as a new tractable host to study infections by animal pathogenic oomycetes. PLoS Pathogens, 17(3), e1009316. https://doi.org/10.1371/journal.ppat.1009316
• Fasseas, M. K., Grover, M., Drury, F., Essmann, C. L., Kaulich, E., Schafer, W. R., & Barkoulas, M. (2021). Chemosensory Neurons Modulate the Response to Oomycete Recognition in Caenorhabditis elegans. Cell Reports, 34(2), 108604. https://doi.org/10.1016/j.celrep.2020.108604