Dr Varsha Singh

Research interests

Olfaction and odours

Odours are produced by most microbes and many plants. They are small molecules (300 Da or less) bearing alcohol, aldehyde, ester, aldehyde groups or containing cyclic moieties. They originate from common primary metabolites using unique enzymes encoded in microbial genomes. They serve as signals for intra species, inter species and interkingdom signals. They can also be antimicrobial, antiparasitic agents and pathogen associated molecular patterns [Prakash EMBO J 2021]. 

Olfaction is the most ancient sensory modality but relatively poorly understood. Elephants have 2000 Odorant receptors (ORs), humans have 400 and a worm has close to 400. They make up 3% of all the genes in the human genome. Odorant receptors (ORs) are present not only in our nose but also in out intestine, lungs, kidney, pancreas, liver and other tissues where they might help in sensing the resident community of microbes called the ‘microbiome’.

Fundamental research in our lab

How are odours made? 

Does odour landscape of microbiome changes in ageing mice?

Mechanistic bases of GPCR-odour interactions

Deorphanizing olfactory GPCRs 

Translational research in our lab

Biomarker Discovery Project: 

Odours as biomarkers of infection, neurodegenerative diseases and cancers

E-nose for infectious disease: 

Electronic nose for sensing biomarkers of pulmonary infection in exhaled breath

Approaches

Odour identification: using gas-chromatography mass spectrometry (GC-MS/MS) in combination with microbial genetics. 

GPCR studies: 

We utilize Caenorhabditis elegans, a round worm

1. to understand pathogen recognition via ORs which might serve as non-canonical PRRs,
2. to identify and study ORs involved in regulation of metabolism and longevity,
3. to study function of ORs of humans and mice. 

We utilize multidisciplinary approaches to identify microbe associated molecular patterns from pathogens and microbiota (of worms, mice and human) and their sensing by ORs. We use genetic tools (gene editing via CRISPR, RNA interference and transgenesis), behaviour analysis, imaging and Alpha Fold to identify and manipulate OR signalling in C. elegans. We also focus on identifying microbial odours which are microbe associate molecular patterns (MAMPs) using gas-chromatography mass spectrometry (GC-MS/MS) in combination with microbial genetics. 

What else?

We utilize Pseudomonas aeruginosa, a Gram-negative bacterium, to understand how it utilizes its large genomic repertoire of histidine kinase sensors to identify and compete with other microbes, in the context of respiratory infections including pneumonia. 

Who we are

Our group has one postdoctoral fellow, 4 PhD students and 2 honours students apart from Varsha. We welcome others interested in olfaction and odours to join us. Apart from really pleasant odours (some offensive ones), we do have a lovely view of river Tay from our lab.

Our collaborators

• Dr Changchun Chen, University of Umea, Sweden (GPCR deorphanization project)
• Dr Charis Marwick, UoD (Biomarkers Discovery project on E. coli bacteraemia)
• Dr Sarah Martins da Silva, UoD (Biomarkers Discovery project for women’s health and unexplained infertility)

Open positions

Postdoctoral Fellow We welcome applicants for postdoc positions in our research group. If you are interested in any of the following areas, write to Varsha at [email protected]

• Olfaction, odorant GPCRs and metabolism
• Genetic basis of Anosmia in Parkinson’s Disease
• Odours as biomarkers of chronic, inflammatory disease and of infectious diseases
• Electronic nose for odour biomarkers of disease

If you are interested in working at the cross section of microbiology, immunology and neuroscience, do get in touch.  

PhD Openings will be advertised on this webpage.

M Res Openings can be found at https://www.dundee.ac.uk/postgraduate/life-sciences-msc-research/teaching-and-assessment#projects

Select publications

See Google scholar page for a full list of publications at https://scholar.google.com/citations?hl=en&user=TNeCGC8AAAAJ&view_op=list_works  

Siddiqui R., Mehta N., Ranjith G., Felix M.A., Chen C., Singh, V. Olfactory basis for essential amino acid perception during foraging in Caenorhabditis elegans.

DOI: 10.7554/eLife.101936.1

Venkatesh, S., Siddiqui R., Sandhu, A., Ramani, M., Houston I.R., Watts J.L., Singh, V. Homeostatic control of stearoyl desaturase expression via patched-like receptor PTR-23 ensures the survival of C. elegans during heat stress. 

PLoS Genet. 2023 18;19(12):e1011067 

DOI: 10.1371/journal.pgen.1011067 

Badal, D., Kumar, A., Singh, V., Danny, R. A dynamic fluid landscape mediates the spread of bacteria.  arXiv:2309.05351 

DOI: 10.48550/arXiv.2309.05351
Ambreetha, S., Singh, V. Genetic and environmental determinants of surface adaptations in Pseudomonas aeruginosa.     Microbiology 2023 169 (6), 001335

DOI: 10.1099/mic.0.001335 

Venkatesh, S., Singh, V. Amphid Sensory neurons of Caenorhabditis elegans orchestrate its survival from broad classes of pathogens. Life Science Alliance 2023 6 (8)

DOI: 10.26508/lsa.202301949 

Pradhan, D., Tanwar, A., Parthsarathy, S. and Singh, V. Toroidal displacement of Klebsiella pneumoniae by Pseudomonas aeruginosa is a unique mechanism to avoid competition for iron.

bioRxiv (preprint) https://doi.org/10.1101/2022.09.21.508880

Filipowicz, A., Aballay, A., Singh, V. Cellular and Organismal Responses to Infections in Caenorhabditis elegans. Elsevier 

DOI:10.1016/B978-0-12-821618-7.00043-2. 

Prakash, D., Siddiqui R., Chalasani S., Singh, V. Pyrrole produced by Pseudomonas aeruginosa influences olfactory food choice of Caenorhabditis elegans.  

bioRxiv (Preprint)      https://doi.org/10.1101/2022.01.27.477966

Badal, D., Jayarani, A.V., Kollaran, M.A., Prakash, D., Monisha P., Singh, V. Foraging signals promote swarming in starving Pseudomonas aeruginosa. mBio 2021, 12(5):02033-21.

https://doi.org/10.1128/mBio.02033-21 

Prakash, D., Akhil, M.S., Radhika, B., Venkatesan, R., Chalasani, S.H., Singh, V. 1-Undecene from Pseudomonas aeruginosa is an olfactory signal for flight or fight response in Caenorhabditis elegans. EMBO J. 2021, e106938. 

https://doi.org/10.15252/embj.2020106938 (OPEN ACCESS)

Sandhu, A., Badal, D., Sheokand, R., Tyagi, S., Singh V. Specific collagens maintain the cuticle permeability barrier in Caenorhabditis elegans. GENETICS 2021, 217(3):iyaa047. 

https://doi.org/10.1093/genetics/iyaa047 (OPEN ACCESS)

Venkatesh, S.R., Singh, V. G protein-coupled receptors: The choreographers of innate immunity in Caenorhabditis elegans. PLoS Pathog 2021, 17(1): e1009151. 

https://doi.org/10.1371/journal.ppat.1009151 (OPEN ACCESS)

Dixit, A., Singh, V. The brain-gut axis of longevity. Aging (Albany NY) 2020,12(18):17754-17755. doi: 10.18632/aging.103996. Epub ahead of print. PMID: 32986014; PMCID: PMC7585115. 

Prakash, P., Abdulla A.Z., Singh, V., Varma, M.M. Swimming statistics of cargo-loaded single bacteria. Soft Matter 2020, 100: 062609. 

Dasgupta, M., Shashikanth, M.,  Gupta, A.,  Sandhu, A., De, A., Javed, S.,  Singh, V.  NHR-49 transcription factor regulates immuno-metabolic response and 1 survival of Caenorhabditis elegans during Enterococcus faecalis infection. Infec Immun. 2020, 88(8):e00130-20 (full text)

https://doi.org/10.1128/IAI.00130-20 (OPEN ACCESS)

Dixit, A., Sandhu, A., Modi, S., Shashikanth, M., Koushika, S., Watts, J., Singh, V. Neuronal control of lipid metabolism by STR-2 G protein-coupled receptor promotes longevity in C. elegans. AGING CELL 2020, 19(6):e13160 (full text)

https://doi.org/10.1111/acel.13160  (OPEN ACCESS)

Kollaran, M.A., Joge, S., Harshitha, K., Badal,  D., Prakash, D., Mishra, A., Varma, M.M. and Singh, V. Context-Specific Requirement of Forty-Four Two-Component Loci in Pseudomonas aeruginosa Swarming. iScience. 2019 Mar 29;13: 305-317. 

https://doi.org/10.1016/j.isci.2019.02.028
Gupta, A., Singh, V., (2017). GPCR Signaling in C. elegans and Its Implications in Immune Response. In Advances in immunology (Vol. 136, pp. 203-226). Academic Press. [Book Chapter], doi: 10.1016/bs.ai.2017.05.002

Sun, J., Singh, V., Kajino-Sakamoto, R., Aballay, A. Neuronal GPCR controls innate immunity by regulating non-canonical unfolded protein response genes. Science 2011, 332(6030):729-32. doi: 10.1126/science.1203411.

Styer, K.L., Singh, V., Macosko, E., Steele, S.E., Bargmann, C.I., Aballay, A. Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR. Science 2008, 322(5900), pp.460-464. doi:10.1126/science.1163673

Singh, V., Aballay, A. Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proceedings of the National Academy of Sciences 2006, 103(35), pp.13092-13097. doi:10.1073/pnas.0604050103