Mechanism and Regulation of Nuclear Expansion:
Our group is addressing two major questions in nuclear expansion using Tetrahymena thermophila as a model organism.
1) Mechanism of nuclear expansion
The nucleus is a membrane-bound organelle that undergoes dramatic changes in size and shape during cell cycle progression. One such change is fragmentation of the nuclear envelope (NE) during mitosis. This fragmentation is a specific feature of metazoans. In yeast, for example, a "closed" mitosis without NE fragmentation requires nuclear membrane expansion to allow chromosome separation within a single intact nucleus. A more general change is the expansion of the NE in post-mitotic cells to accommodate chromatin de-condensation and DNA replication. Nuclear remodeling is a complex process requiring coordinated biosynthesis, targeting and interaction of the nuclear membrane with nuclear pores, inner nuclear membrane proteins and chromatin. How this is accomplished is not clearly understood in any system.
We use Tetrahymena thermophila as a model system to study nuclear remodeling. The unicellular, free-swimming ciliate undergoes closed mitosis, as does yeast. A striking advantage of Tetrahymena is that, nuclear envelope expansion in this organism occurs to a dramatic extent (~10-15 folds) during specific stages in cell conjugation; a process that can be highly synchronized in cell cultures. We have recently discovered that dynamin related protein 6 (Drp6) is required for nuclear remodeling in Tetrahymena. However, the mechanism by which Drp6 performs its function is not known. Therefore, one important objective is to understand the mechanism of Drp6 function in nuclear remodeling.
2) Cell cycle regulation of lipid homeostasis and membrane biogenesis
Nuclear expansion is a regulated process that occurs at a particular stage of cell cycle. A phosphatidic acid phosphatase (PAH1) regulates nuclear expansion in yeast by undergoing phosphorylation and dephosphorylation. While phosphorylated form of PAH1 is involved in nuclear expansion, its dephosphorylated form inhibits the process. The phosphorylation and dephosphorylation state of PAH1 is regulated by cell cycle related kinase (Cdk1) and phosphatase (Nem1 and Spo7 complex) respectively. We have established the role of large PAH1 homologue in lipid homeostasis and maintaining ER tubular structure in Tetrahymena and observed functional conservation with yeast homologue. However, the regulation of PAH1 is not known in Tetrahymena. We found three Nem1 homologues and would address their role in regulation of nuclear expansion, lipid homeostasis and ER structure. Since we did not find any homologue of SPO7 in Tetrahymena, we would also try to identify the protein performing the similar function in this organism.
The contemporary distribution of biota within the Indian subcontinent must have been shaped by its unique history. The Indian subcontinent was part of Gondwanaland and had close tectonic associations with Africa, Madagascar and Seychelles before eventually colliding with Eurasia, resulting in the orogenesis of the Himalayas. The initial contact of the Indian plate with Southeast Asia may have potentially resulted in exchange of biota across these two landmasses. On the other hand, the contemporary Indian subregion reusers insular from other biogeographic zones areas owing to various geographic barriers. Prolonged insularity generally promotes diversification in lineages with limited dispersal ability, resulting in endemic radiations. Beyond bearing these unique spatial and temporal signatures in its biotic assembly, the Indian subcontinent itself is heterogeneous in its topography with about ten major river systems/ basins flowing out of the peninsula. Additionally, the Indian subcontinent has about six major hill ranges. Cumulatively, these factors would have had (or still have) a significant effect on the contemporary distribution of biota within the Indian subcontinent, resulting in an interesting mix of lineages. Indian biota may therefore be composed of ancient Gondwanan relicts to lineages that dispersed more recently from other regions. I am personally interested in South Asian herpetofauna (reptiles and amphibians), largely owing to their diversity and antiquity. However, in my lab we have a set of broad interests ranging from understanding systematics, biogeographic patterns and evolution of characters in a diverse range of taxa from the Indian subcontinent. As a lab PI, I want to usertain and inculcate a keen interest in organismal biology, ecology, natural history, systematics and biogeography.
Host-pathogen interactions, cell signalling events, immunopathogenesis of infection, cancer microenvironment, molecular events in cancer metastasis and apoptosis.
With the shifting demographics towards older age, there is a major concern for age-related disorders. 90% of individuals dying each year are due to age-related causes. Understanding the genome, epigenome and proteome between healthy and diseased state of these individuals pave a way for unravelling bio-markers for early diagnosis and/or therapeutics for various diseases. Our goal is to find these underlying players that change the micro-environmental niche differently in a diseased state during the developmental process of aging and hence are responsible for these age related-disorders. We are currently focusing on understanding the pathomechanism of two neurodegenerative eye disorders (Glaucoma, the leading cause of irreversible World Blindness and Corneal Endothelial Dystrophies) as well as Cancer using a pleothora of cellular, biochemical, genetics, genomics and molecular biology techniques involving human samples, Drosophila models as well as in vitro cell lines.
Studies on antibiotic resistance and virulence in gram negative bacteria
Signaling Systems in Plants, Light perception, flowering time control, circadian rhythm and biological clock.
Agricultural Biotechnology
My research broadly focuses on the regulation of tumorigenesis and tumor angiogenesis. Specifically, I aim to identify novel molecular regulators involved in cancer progression, with an emphasis on uncovering therapeutic targets that are inherently less susceptible to drug resistance.
The following two broad problems are currently being pursued in the lab using a combination of in vitro reconstitution, cell-based experiments, advance fluorescence microscopy/spectroscopy, computational and micro-manipulation tools:
1) We are interested in understanding the interplay of cellular membrane parameters and the kinetics of aggregation of intrinsically disordered proteins (IDPs) such as Amyloid-beta, full-length human Tau and alpha-Synuclein. This will help us understand how different IDPs and host cellular membranes influence each other in terms of aggregation kinetics of the IDP or the changes in the physico-chemical parameters of the cellular membranes that might eventually drive neuronal membrane deformation resulting in neurodegeneration and propagation of amyloids from cell to cell.
2) Mechanism by which Mycobacterial secretory components manipulate host cellular membranes to evade phagosome maturation.
Prof. Palok Aich is widely regarded for his innovative work at the intersection of biophysics, immunology, and microbiome science, contributing significantly to both fundamental research and its practical applications in health and disease management. With a foundational background in biophysics and molecular biology, he integrates multi-omics technologies, AI/ML-based analytics, and animal models to understand how the gut microbiome influences host metabolism, inflammation, and neuro-immunological health.
Introduction and Research Overview
Introduction
Prof. Palok Aich currently serves as the Dean of Research & Development at the National Institute of Science Education and Research (NISER), India, and is the Director of both the NISER Homi Bhabha Foundation and MicrobioTx Health. Prof. Aich holds a Ph.D. in Biophysics from the Saha Institute of Nuclear Physics and has extensive international experience, having held research and leadership positions in Canada before joining NISER in 2009.
Research Overview
Areas of Focus
Prof. Aich’s multidisciplinary research centers on understanding the profound relationship between the gut microbiome, host metabolism, immunity, and brain health. His work integrates multi-omics technologies, artificial intelligence and machine learning (AI/ML) analytics, animal models, and human studies to:
Innovations and Impact
Selected Achievements
Research Interests
Main Interests | Key Topics |
Gut Microbiome | Gut-Adipose-Brain Axis, Host-Microbial Interactions1 |
Metabolomics & multiomics | Metabolome-microbiome correlation for IBD, NAFLD, T2D, Obesity, Psychological Stress, Neurodegeneration |
Innate Immunity | Mucosal & systemic immune responses, stress physiology |
Bioinformatics & AI | Predictive modeling, data mining, personalized medicine |
Translational Biomedicine | Non-invasive diagnostics, precision probiotics, entrepreneurship |
Prof. Palok Aich’s innovative, integrative approach positions him as a pioneer in translating foundational science to real-world health solutions. His leadership at NISER continues to advance the frontiers of life sciences in India and beyond.
Research Focus and Main Contributions
Research Focus
Prof. Palok Aich is recognized for his pioneering interdisciplinary work bridging biophysics and microbiome studies. His research centers on:
Main Contributions
Summary Table
Area | Key Contributions |
Biophysics | Discovery of M-DNA; bio-imaging innovation; systems approaches to molecular biology |
Microbiome Studies | Gut Function Test (GFT); personalized probiotics; gut-brain axis research |
Data Science & AI | Predictive models for disease; network analysis of microbiome-metabolome links |
Translational Medicine | Non-invasive diagnostics; public health tools for metabolic, inflammatory, and neurodegenerative diseases |
Prof. Palok Aich’s unique integration of biophysics and microbiome research has led to breakthroughs with practical impact in diagnostics, therapeutics, and personalized medicine, marking him as a leader in his field.
Key Findings from Palok Aich's Research on Microbiome Influence in Metabolic Diseases
1. Gut Microbiota Shapes Systemic Metabolism
2. Microbiome Composition and Dysbiosis
3. Impact on Metabolic Disease: Obesity, Diabetes, NAFLD
4. Translational Innovation
5. Critical Developmental Windows
6. Integration of Multi-Omics and AI
Summary Table: Major Research Findings
Area | Key Findings |
Microbial Metabolites | Induce adipose browning, enhance lipid metabolism |
Microbiome Composition | Shifts (Firmicutes/Bacteroidetes ratio, fat/starch diet impact) linked to metabolic outcomes |
Disease Links | Dysbiosis drives or ameliorates obesity, diabetes, NAFLD, based on species and metabolite changes |
Probiotics/Diagnostics | Precision probiotics and blood-based microbiome tests enable targeted, individualized interventions |
Early-Life Microbiome | Postnatal gut changes shape future metabolic and immune health |
Palok Aich’s research demonstrates a strong, causative relationship between the gut microbiome, its metabolites, and the risk and regulation of metabolic diseases, positioning microbiome-targeted therapies as a promising frontier in personalized medicine and chronic disease management1,3,5.
Our work is being widely cited by the media. A few to mention are BioVoiceNews, OnlyMyHealth, BioSpectrum, Nuffoodsspectrum, DBT-ILS, Nextedge, ANI, NEWSVOIR.
Pre-NISER Career Highlights
Academic Training and Early Research
Research in Canada
Principal Investigator at VIDO (Canada)
Recognition and Legacy
References:
In 2009, we returned to India. When I left VIDO, I had seven ongoing projects funded by various Canadian Funding Agencies. I could not bring these funds, for obvious reasons, to India. I then transferred those projects to other faculty members at VIDO.
In 2009, I joined NISER as an Associate Professor and started understanding the effects of psychological stress on humans to develop programs on innate mucosal immunity
The fundamental difference between prokaryotic and eukaryotic translation initiation is that the former uses Shine-Dalgarno (SD) sequence on the mRNA to recruit small ribosome subunit and locate AUG codon or rarely GUC, CUC or UUG codon as a translation start site, while the latter uses eIF4F complex to bind mRNA and locate AUG codon or rarely CUG, UUG or GUC as a start codon by 5` to 3` scanning mechanism. Some of the examples listed below shows the involvement of non-AUG codon as a translation start signal.
In Saccharomyces cerevisiae, GRS1 encodes two isoforms of Glycyl-tRNA synthetases, one initiates from upstream in-frame UUG codon (encoding signal sequence for mitochondrial import) while the regular cytoplasmic version initiates from downstream AUG codon. For the synthesis of Alanine t-RNA synthetase (ALA1) protein a consecutive ACG ACG codon are utilized as an alternate translation start site. It has been reported recently that MHC class-I molecule can load antigenic precursor which is synthesized by using CUG as an initiation codon recognized by leucine tRNA and non-conventional eIF2A translation initiation factor. A genome wide ribosomal profiling analysis of vivo translation study reported that translation initiation from upstream non-AUG codon is widespread in S. cerevisiae under starvation condition. However, the importance and the basic mechanism for these initiations are still unclear. A number of yeast mutants have been identified that are able to initiate at the non-AUG codons. These mutants were designated as Sui— (Suppressor of initiation) phenotypes. Sui— phenotypes are novel mutations that causes break down of AUG codon selection fidelity. Thus, Sui— mutants provide an important tool to understand the molecular mechanism of non-AUG codon selection.
The focus of our lab is to understand the molecular mechanism of non-canonical translation initiation processes in Saccharomyces cerevisiae using molecular genetic techniques.
The key questions are as follows:
Neural circuits and behavior, Neuroendocrine regulation
What I cannot create, I do not understand
- Richard Feynman
So is true for Life. For nearly a century, it was believed that Humans and its close relatives such as yeast and other eukaryotes were the sole owners of the Cytoskeleton, a mechanical framework that supports cells and carries almost all essential process within. However, recent discoveries have proved this to be a myth and shown us that the cytoskeleton was an innovation of our distant ancestors - 'Bacteria'. The bacterial cytoskeleton provides the most simplistic framework to understand the mechanical basis of all cellular process such as spatial organization and compartmentalization, cell shape establishment, cell movement, DNA segregation and cell division that are vital to the propogation of life. One of the most fascinating aspects of the cytoskeleton is their remarkable ability to self-organize and assemble into a great diversity of dynamic structures.
Broadly, our research interests lie in evolution of self-organisation, form and function in biological systems and in understanding the means by which bacterial pathogens have exploited this organization in pathogenesis for their survival and reproduction. In our research laboratory, we aim to understand how tiny cells such as bacteria achieve cellular organization and how the mechanical properties of their cytoskeleton allow them to perform the cellular functions.
We pursue these research interests through studying the following process in life:
• Cell division and Spatial organization in Bacteria - Bacterial cytoskeleton dynamics, Cytokinetic ring assembly, Regulation of cell division control and anti-bacterials targeting bacterial cytoskeleton.
• Bacterial Metabolism & Biofilms - Molecular pathways by which Bacterial proteases regulate lipid metabolism & biofilm formation.
• Bacterial Pathogenesis - Molecular Mechanisms of Bacterial effectors that target and affect Eukaryotic Cytoskeleton and Cell Cycle.
• Synthetic Biology - Synthetic Protein Polymers: Evolution of synthetic cytomotive proteins for use in biological & artificial cell systems.
Given the rapid increase in the rate of multi-drug resistance, there is a resurgence of the once conquered infectious diseases. There is an urgent need for a new class of antibiotics and bacterial cell division has proved to be an attractive target. Thus we are currently actively focused on regulation of cell division and spatial organization in bacteria. We also have an ongoing effort on creating "synthetic cytomotive proteins" for use in artificial cells.
Evolutionary Ecology Lab (EEL@NISER)
I am an evolutionary ecologist interested in understanding the forces and mechanisms that shape an organism's evolutionary trajectory. Rapidly changing anthropogenic stressors introduce novel selection pressures, leading to biodiversity loss and the emergence of new coping mechanisms in certain species. The biotic interactions among communities, populations, and individual organisms are central to this adaptation, which drives evolutionary processes. Modern sequencing techniques have shown that these interactions extend beyond the macroscopic world, significantly influencing microbial communities as well. At the intersection of these realms, macroscopic hosts and their associated microbes interact, shaping each other's evolutionary paths.
My research aims to trace these biotic interactions at various organizational levels, from host communities to individual hosts, host-microbiome interactions, and microbial communities, to understand their impact on organismal evolution. By employing classical eco-evolutionary approaches and utilizing both wild and laboratory-reared insect populations as model systems, my lab is interested in uncovering how organisms adapt to novel and rapidly changing selection pressures.
Project 1: Impact of anthropogenic noise on biodiversity and ecosystem health - estimating the threat and potential coping mechanisms
The health and sustainability of an ecosystem depend on its biotic organisation. A diverse ecosystem is a good indicator of its health, as biodiversity provides resilience and redundancies that are key to ecosystem functioning. Hence, threats to biodiversity, in the form of human activities, can lead to the functional collapse of an ecosystem. Unfortunately, most research on biodiversity is patchy, intrusive, biased towards charismatic taxa, and often overlooks elusive and nocturnal species. Since over 50% of organisms, including diurnals, rely on acoustics for communication, passive recording can provide an efficient, non-invasive, yet less biased estimate of biodiversity. However, acoustic communication suffers from an omnipresent, pervasive threat, anthropogenic noise.
Most organisms use acoustics for conspecific recognition, competition, and mate choice. This communication has evolved under conspecific and heterospecific masking (signal overlap) giving rise to coping mechanisms like spatial, temporal, spectral (pitch) separation of signallers, and selective hearing in receivers. Anthropogenic noise, which has no particular signal structure, can act as a novel selection pressure by altering the complexity of masking, rendering the existing coping mechanisms ineffective. This can lead to a communication breakdown and large-scale loss of species diversity.
We aim to understand how acoustically communicating communities cope under such pervasive anthropogenic stress. Since insects are the most diverse yet understudied taxa, we aim to use their diversity as an indicator of ecosystem health. Among insects, Ensiferans (crickets and katydids) are one such taxa that are present across a variety of habitats and have mesmerising acoustic diversity and complexity. Unfortunately, these insects are poorly studied, with almost no data on their diversity and distribution along eastern India. We aim to study the impact of anthropogenic noise on their diversity, communication patterns, and potential coping mechanisms to ascertain the threat level in these habitats.
Structural biology of soluble and transmembrane proteins, and De novo design of proteins.
Proteins are workhorses of a cell, engaged in a wide range of tasks comprising structural stability, cell signaling, catalysis, transporting, molecular printing, membrane fusion, regulation, etc. Understanding the mechanism that underlies the functioning of these molecular gadgets is an intriguing question, and defines the fundamentals of biological processes. This is an interdisciplinary research program as we set out to address the question using X-ray crystallographic methods coupled with biophysical, biochemical and computational approaches.
Our structural biology group aim to deduce the structure based mechanism for the functioning of cation selective channels from viruses. The structures not only enhance our current knowledge, but also provide leading point for the structure based drug design. Also, we are interested in the structural biology of bacterial two component systems, a wide spread signal transducers.
Our other research program is de novo protein design, which aim to put our understanding of principles that define protein folding and functioning into test. Here, we seek to design scaffolds that are tailored to have predetermined non-covalent interactions as well as functions.
Research Theme: The fundamental consequences of cellular responses associated to altered physiological processes during infection, cancer and/or tumor progression, inflammation and immunogenic responses in various cases of altered host cell functions and phenotypes are the prime interest of our ongoing research.
We have been working in the field of host cell responses and cellular immunology with special interest of ongoing immune-regulatory responses, cellular function and phenotypes associated to Cell mediated immunity (CMI) of T cells and accessory antigen presenting cells. Currently, we have major interest groups within NISER and also with external collaboration, where we are investigating functional expression of Toll like receptor (TLR) and Transient Receptor Potential Vanilloid (TRPV) Channels in cell mediated immunity (CMI), analyzing cellular and immunological response(s) of host cells during experimental Chikungunya virus (CHIKV) infection along with anti-cancer immunity as major projects.
In brief, our research focuses to dissect out the important roles of cellular and immunological aspects to decipher the cellular pathways, strategies associated to altered host cell responses for an ongoing infection, tumor progression, inflammation-immunity and immuno-regulatory processes associated to diseases biology in different contexts of cellular responses. Research with cell lines, primary cells, animal model and also with the human blood samples from normal donors and patients with due consents and National guide lines are the prime components for such experimental studies. Such understanding will be helpful towards designing immuno-therapeutic strategies to control various diseases.
Our research focusses on-
1. Elucidating pathophysiological mechanisms of neurological disorders focusing on ion channels.
2. Creating novel brain models using human induced pluripotent stem cells (hiPSCs) from patients
to study neurological disorders.
3. Translating novel mechanisms to develop therapy against neurological diseases.
List of Publications
Google scholar link- https://scholar.google.com/citations?user=xsEnuCEAAAAJ&hl=en
My research interest is to understand structure-function relationship of viral proteins in viral entry, genome replication and packaging into capsids.
Cell-entry of alphaviruses: Chikungunya virus, an aedes mosquito-transmitted alphavirus, enters cells through receptor-mediated endocytosis, and membrane fusion in acidic pH of endosome. Two viral surface proteins, E1 and E2 facilitate entry process. E1 'pulls' apposing endosomal and cell membranes close enough, after endosome acidification, so that they fuse and open a pore. My lab is interested in understanding the acidic-pH triggering mechanism for E1 and structural changes in the protein that lead to membrane fusion.
Nucleic acid packaging in dsDNA viruses: Viruses with double stranded DNA genome pack DNA into capsids at very high densities. Some bacteriophages Human herpesviruses (one of those with large genomes) pack their genome into pre-formed capsid through concerted action of a portal complex and terminase complex. Terminase complex of herpesviruses can be a good drug-target. My lab studies structure-function relationship of terminase protein complex components to explain the mechanism of action of the complex.
Replication complexes of flaviviruses: another interest in the lab is on replication complexes of flaviviruses. Dengue virus, a member of the virus family, forms a complex of more than five different proteins (nsp1,2a, 2b, 3, 4a, 4b and 5) formed from a single polyprotein through proteolytic processing. Special membrane-bound replication complexes are formed from ER membrane surface and viral RNA is amplified inside these vesicles. We aim to characterize these complexes and study interactions amongst the proteins in complex.
Rational drug discovery and development require a streamlined, interdisciplinary effort from researchers working in specialized areas. From active collaboration, the drug discovery process can be and has been significantly shortened by addressing bottlenecks in drug discovery (off-target effects, polypharmacology, and chemoresistance). Our research focuses on some unanswered questions that could contribute to the development of chemotherapy.
Establishing the bioactivity of a lead molecule (of any origin) from an in vitro study is the start of a long journey in the drug discovery pipeline. The pharmacological effect of the lead molecule observed in vitro may not directly correlate with the in vivo results due to the molecule's physicochemical properties, bio-pharmacokinetics, or structural mimicry. Here, we try to design suitable study models (in silico, in vitro, and/or in vivo) that can progressively help develop a reliable formulation.
The following are the areas and related publications we presently focus on: