Dr Nikhil Jain PhD

Nikhil Jain

Institute of Inflammation and Ageing
Assistant Professor
Birmingham Fellow

Contact details

Address
Institute of Inflammation and Ageing
University of Birmingham Research Labs
Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2WB

Nikhil Jain is a Birmingham Fellow working across the Institutes of Inflammation and Ageing, and the School of Chemical Engineering. Nikhil is a cell engineer who specializes in mechanobiology and developing novel bioengineering tools and techniques and combining them with cutting-edge epi-imaging, and advanced “omics” to tackle challenging questions in human health. 

Research in Nikhil’s lab (Mechano-theranostics lab (MeTL)) is at the interface of engineering, cell mechanics, and medicine and mainly focuses on applying fundamental mechanobiology-based principles to better understand human ageing and age-associated inflammatory diseases. The long-term goal is to couple changes in mechanical properties of aged cells with altered nuclear mechano-epigenomics programs to uncover novel mechano-signaling pathways to treat age-associated inflammatory diseases. The lab also focuses on developing new engineering techniques to develop bioengineered devices to better diagnose age-associated inflammatory diseases at the single-cell level. 

Google Scholar ID

ORCID

Qualifications

  • Doctor of Philosophy (PhD), National University of Singapore, 2008-2014
  • Bachelor of Technology (B. Tech), Industrial Biotechnology, India, 2003-2007

Biography

Nikhil Jain is a bioengineer with strong expertise in a wide range of techniques applied to address fundamental and translational biological problems. He considers himself an interdisciplinary researcher as he has worked at the interface of bioengineering, mechanobiology, and epigenetics.

During his Ph.D., by sculpting single cells of varied shapes, sizes, and aspect ratios, he has shown how the geometrical constraints impinge on nuclear morphology, actomyosin contractility, chromatin compaction, and thus gene expression. By generating multi-dimensional plots, he linked specific gene clusters with distinct cell geometries. Using high-resolution imaging and fluorescence correlation spectroscopy, he also provided the underpinning mechanisms of geometry guided transcriptional regulation.

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During his postdoc period, he has contributed to the formulation of a new paradigm of inflammatory gene expression regulation of macrophages by mechanical forces, which exist in healthy and diseased tissues. He developed novel bioengineered surfaces to apply confinement on single macrophages, which tunes the transcriptional programs and thereby alter the inflammatory state of macrophages.

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In 2017 and then in 2018, he was awarded SNF and EMBO research visit grants respectively to spend time at the Tel-Aviv University, Israel to use novel epi-imaging techniques to understand changes in DNA epigenetics modifications during macrophage inflammation.

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The results of his research were published in major journals: Nature Materials, PNAS, NAR, Epigenetics, etc. His area of mechanoimmunology includes immunology, age-related disease, material sciences, and bioengineering. In 2019, he was promoted to the position of Junior Group Leader at the Institute of Translational Medicine at ETH Zurich and was awarded an SNF SPARK grant to characterize changes in mechanics of aged immune cells and how to tune their hyperinflammatory activated state.

In 2021, Nikhil moved to the University of Birmingham with a goal to establish a novel transdisciplinary research field of mechanobiology, bioengineering, inflammation, and ageing and ultimately, achieve fundamental and translational success targeting human ageing processes and associated inflammatory diseases.

Teaching

Frontiers in Nanotechnology at ETH Zurich

Postgraduate supervision

Previously supervised one PhD student and always looking for highly motivated, science driven, and hardworking people to join our team.

Ph.D. and MSc Research Students

Applications are welcomed from candidates who wish to study for a Ph.D. in the broad field of mechanobiology and bioengineering. We are also pleased to support exchange of doctoral students nationally and internationally. Please contact Dr. Jain to discuss possible Ph.D. and MSc research opportunities. Funded positions will be advertised on findaphd.com

For any research enquiries, please email: n.jain@bham.ac.uk

Research

Our group is interested in three independent yet interconnected areas:

Mechano-genomics of human ageing

Human ageing is associated with changes in the mechanical and biophysical properties of cells and their microenvironment. However, how these mechanical changes in cells’ intrinsic and extrinsic properties regulate their genomic and epigenomic profiles is poorly understood. We study how aging affects the biophysical properties of immune cells, mainly macrophages, T-cells, and neutrophils, and how these changes alter their inflammatory genomic programs and the underlying transcriptional and epigenetic regulators. To address this, we combine high-resolution imaging with an advanced single-cells “omics” toolkit and cutting-edge single-molecule epi-imaging.

Mechano-diagnostics of inflammatory diseases

The early detection of severe inflammatory diseases allows for a more rapid and effective therapeutic treatment with a correspondingly more favourable clinical outcome. However, diagnosis of such inflammatory conditions suffers from major shortcomings, most notably the time-consuming measurements (cytokine measurement), that delay the rapid deployment of antibiotics, the requirement of a large volume of blood samples, and lack of Point-of-Care tests. Therefore, an urgent need exists for methods of advanced detection of inflammation based on novel biomarkers and using techniques that are faster and easier to be implemented sufficiently early to allow effective intervention and prevention, yet also have satisfactory sensitivity. Towards this, our lab combines fundamental and advanced engineering approaches with translational immune-ageing to develop mechanical fingerprints, which are sensitive and easy to implement, to better diagnose age-associated diseases.

Mechano-therapeutics to reduce age-associated inflammation

Our lab is interested in finding novel targets to restore the original mechanical properties of aged cells to re-establish healthy genomic confirmation to tame age-associated inflammatory diseases. We also plan to target novel mechanosignaling pathways, that we have recently identified, to tune inflammatory activation of immune cells during ageing and age-associated diseases.

Other activities

Junior Group Leader and Lecturer (Aug 2019-till now)

Department of Health Science and Technology, ETH Zurich, Switzerland       
Research Focus: Immuno-engineering, and Mechano-genomics in inflammation, and human ageing

SNF Visiting Research Fellow (Dec 2020-Mar 2021)

Institute of Inflammation and Ageing, University of Birmingham, U.K.
Project: Targeting mechanical properties of immune cells to reduce inflammation and sepsis

Post-Doctoral Associate (Sept 2014-Aug 2019)                                             

Department of Health Science and Technology, ETH Zurich, Switzerland
Project: Mechano-Immunology and Mechano-Engineering of macrophage polarization

Visiting Research Fellow (Feb 2019-Mar 2019)

Weill Institute for Cellular and Molecular Biology, Cornell University, USA
Project: Probing mechanical properties of nucleus during macrophage inflammatory activation

SNF (Apr 2017-Jul 2017) and EMBO (Jul 2018-Sept 2018) Research Fellow

Department of Chemical Physics, Tel-Aviv University, Israel
Project: Epigenetic profiling during inflammation using Super-Resolution Genome Mapping

Visiting Research Fellow (Oct 2017-Nov 2017 & Nov 2018-Dec 2018)

Department of Chemistry, University of Chicago, USA
Project: RNA modification during macrophage inflammation and disease

Visiting Research Fellow (Feb 2014-Aug 2014)                                 

Woods Hole (MBL) and Feinberg School of Medicine, Northwestern University, USA
Project: Mechanics of intermediate filaments in giant axonal neuropathy patient

Publications

  1. Mehl J., Earle A. Lammerding J., Vogel V. and Jain N. Degradation of the nuclear lamina upregulates the pro-inflammatory response of macrophages (under review)
  2. Jain N.**,Shahal T., Gabrieli T., Gilat N., Torchinsky D., Michaeli. Y., Vogel V., and Ebenstein Y.** (2019) Global modulation in DNA epigenetics during pro-inflammatory macrophage activation. Epigenetics 14 (12), 1183-1193 
    In this work, we present methodological advances for globally quantifying DNA epigenetic marks by single-molecule epi-imaging. The combination of techniques is robust, easy to implement, cheap and require only nanogram of starting material thus allowing a holistic picture of DNA epigenetics relevant to any studied system.
  3. Jain N.,Moeller J.,and Vogel V. (2019) Mechanobiology of Macrophages: how physical factors co-regulate macrophage plasticity. Annual Review of Biomedical Engineering 21: 267-297
  4. Jain N.**,and Vogel V.**(2018) Downsizing the inflammatory response of macrophages by cell confinement. Nature Materials 17: 1134-1144
    Using 2D and 3D bioengineered surfaces, this study has identified a novel regulatory mechanism for macrophage activation: “spatial confinement”. I have shown that macrophage confinement suppresses the LPS-induced transcriptional programs by mechanomodulating chromatin-compaction, epigenetic-modifications, and transcription factors. The suppressed biomarkers have been implicated in microbial killing, immune-regulation, and secretion of reactive oxygen species.
  5. Wang Y., Jain N.,Nagarajan M., Maharana S., Iyer KV., Talwar S. and Shivashankar G.V. (2017) Coupling between chromosome intermingling and gene regulation during cellular differentiation. Methods 123: 66-75
  6. Jain N.*, Maharana S.*, Iyer KV. *, Nagaranjan M., Weng Y. and Shivashankar G.V. (2016) Chromosome intermingling—the physical basis of chromosome organization in differentiated cells. Nucleic Acid Research 44(11): 5148-5160
    This work, for the first time, showed that instead of chromosome size and gene density, chromosome intermingling is the physical basis of non-random three-dimensional positioning of chromosome in the interphase nucleus.
  7. Jain N.*, Lowry J*, Edward R., Mahammad S., Opal P., Goldman A., Gelfand V. and Goldman R.D. (2016) Abnormal intermediate filaments organization alters mitochondrial motility in giant axonal neuropathy fibroblast. Molecular Biology of Cell 27(4): 608-616
    In this work, we reported improper Vimentin assembly as a major cause of giant axonal neuropathy, a life-threatening neurological disorder.
  8. Veronika B., Stephen A., Jain N., Gabriel O., Daniel N., Wiesmullar L., Berger S. and Goldman R. D. (2015) Role of Lamin B1 in chromatin instability. Molecular and Cellular Biology 35(5): 884-898
  9. Talwar S., Jain N., and Shivashankar G.V. (2014) The regulation of gene expression during onset of differentiation by nuclear mechanical heterogeneity. Biomaterials 35: 2411-2419
    This study has shown how the nuclear shape heterogeneity can be used as a marker for the early onset of stem cell differentiation.
  10. Jain N., Iyer KV., Kumar A. and Shivashankar G.V. (2013) Cell geometric constraints induce modular gene expression patters via redistribution of HDAC3 regulated by acto-myosin contractility. Proceedings of the National Academy of Sciences 110(28): 11349-11354
    This work has provided the first ever evidence of epigenetic regulation (HDAC3 activity) by cell-geometry cues along with cell-geometry regulated antagonistic relationship between MRTF-A and NF-B. By careful sculpting single-cell geometry and thereby altering nuclear structure, this work has provided an early indication of physical forces guided cellular reprogramming.