Dr Navaneethan Palanisamy

MD5028 Advanced Microbiology 

MD4008 Introduction to Microbiology

MD6030 Medical Microbiology

MD7006 Clinical Immunology and Microbial Pathology

1. Split inteins and applications:

In industries, for the production of recombinant proteins, antibiotics are widely utilized. If multiple plasmids have to be maintained in the expression strains, multiple antibiotics have to be used. This, to some extent, imparts additional cost to the product. Also, adding more antibiotics to the culture media reduces the fitness of the expression strains. To overcome these drawbacks, and to have more protein production, we have developed a plasmid tool using which two plasmids can be stably maintained using a single antibiotic in bacteria (Palanisamy et al. 2019 and 2021). Our tool relies on the function of split inteins. Enzymes conferring resistance towards antibiotics are split into two dysfunctional halves and put one half fused to N-intein in one plasmid and another half fused to C-intein in another plasmid. A functional reconstituted enzyme is produced only in cells that carry both the plasmids. This tool was developed for antibiotics namely, kanamycin (pSiMPlk), chloramphenicol (pSiMPlc), ampicillin (pSiMPla), hygromycin (pSiMPlh), puromycin (pSiMPlp) and spectinomycin/streptomycin (pSiMPls). This tool was further expanded for the selection of mammalian cells using puromycin (Palanisamy et al. 2019). A similar tool will be created for other commonly used antibiotics. Further, this split and splice technology will be expanded for other proteins as well.

2. Characterizing proteins with unknown function in Streptobacillus moniliformis and Pasteurella multocida:

Microbes are ubiquitous and life on this planet very much depends on them. Like two sides of a coin, some microbes help us in our everyday life while some other microbes bring diseases and death. Understanding their cell biology will help us, on one hand, reap benefits out of their vast potential and, on the other hand, bring them under control during infection outbreaks. I will be concentrating on zoonotic bacteria. Many encoded proteins of S. moniliformis (causative agent for rat-bite fever) and P. multocida (range of symptoms) have been assigned with unknown function. Using in vitro, in vivo, and in silico techniques, the biological function(s) of these proteins will be identified (Palanisamy 2018). In the beginning, the localization of the candidate proteins will be studied by microscopy. Using bioinformatics tools, the structure and function of these candidate proteins will be predicted. Potential candidate proteins will be purified and characterized in vitro, and the in vivo biological relevance will be studied.

3. Screening and development of antibacterials and antivirals:

Only a handful of antibiotics and antivirals are available to treat resistant bacterial and viral strains, respectively. We have been studying drug resistance in hepatitis C virus (Palanisamy et al. 2013; Danielsson et al. 2014; Lindström et al. 2015; Palanisamy and Lennerstrand 2018; Palanisamy et al. 2018; Akaberi et al. 2018; Kjellin et al. 2019), human immunodeficiency virus (Kokkula et al. 2016; Palanisamy et al. 2017) and influenza virus (Eckert et al. 2014) for quite a while. We have also identified and validated a few antiviral compounds against Zika virus (Akaberi et al. 2020), dengue virus (Xu et al. 2017), and tick-borne encephalitis virus (Akaberi et al. 2021). In collaboration with researchers from Uppsala University, Sweden, new drugs will be screened and developed against Zika virus, dengue virus, tick-borne encephalitis virus, and SARS-CoV-2. Further, new antibacterials will be screened and developed against zoonotic bacterial diseases.

Lennerstrand J and Palanisamy N*, 2021. Global prevalence of adaptive and prolonged infections’ mutations in the receptor-binding domain of the SARS-CoV-2 spike protein. Viruses 13(10):1974. doi: 10.3390/v13101974. *corresponding author"

Palanisamy N*, Ballestin Ballestin J and Di Ventura B, 2021. Expanding the SiMPl plasmid toolbox for use with spectinomycin/streptomycin. ACS Omega 6(22):14148–14153. doi:10.1021/acsomega.1c00649. *also the corresponding author

Romano E, Baumschlager A, Akmeriç EB, Palanisamy N, Houmani M, Schmidt G, Öztürk MA, Ernst L, Khammash M and Di Ventura B, 2021. Engineering AraC to make it responsive to light instead of arabinose. Nat Chem Biol. doi: 10.1038/s41589-021-00787-6.

Akaberi D, Båhlström A, Chinthakindi PK, Nyman T, Sandström A, Järhult JD, Palanisamy N, Lundkvist Å and Lennerstrand J, 2021. Targeting the NS2B-NS3 protease of tick-borne encephalitis virus with pan-flaviviral protease inhibitors. Antiviral Res. doi: 10.1016/j.antiviral.2021.105074.

Palanisamy N, Öztürk MA, Akmeriç EB and Di Ventura B, 2020. C-terminal eYFP fusion impairs Escherichia coli MinE function. Open Biol. doi: 10.1098/rsob.200010.

Akaberi D, Chinthakindi PK, Båhlström A, Palanisamy N, Sandström A, Lundkvist Å and Lennerstrand J, 2020. Identification of a C2-symmetric diol based human immunodeficiency virus protease inhibitor targeting Zika virus NS2B-NS3 protease. J Biomol Struct Dyn. doi: 10.1080/07391102.2019.1704882.

Palanisamy N, Degen A, Morath A, Ballestin Ballestin J, Juraske C, Öztürk MA, Sprenger GA, Youn JW, Schamel WW and Di Ventura B, 2019. Split intein-mediated selection of cells containing two plasmids using a single antibiotic. Nat Commun 10(1):4967. doi:10.1038/s41467-019-12911-1.

Kjellin M, Kileng H, Akaberi D, Palanisamy N, Duberg AS, Danielsson A, Kristiansen MG, Nöjd J, Aleman S, Gutteberg T, Goll R, Lannergård A and Lennerstrand J, 2019. Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway. Scand J Gastroenterol 54(8):1042-1050. doi:10.1080/00365521.2019.1652846.

Steinmetzger C, Palanisamy N, Gore KR and Höbartner C, 2019. A multicolor large Stokes shift fluorogen-activating RNA aptamer with cationic chromophores. Chemistry-Eur J 25(8):1931-1935. doi:10.1002/chem.201805882.

Akaberi D, Bergfors A, Kjellin M, Kameli N, Lidemalm L, Kolli B, Shafer RW, Palanisamy N and Lennerstrand J, 2018. Baseline dasabuvir resistance in Hepatitis C virus from the genotypes 1, 2 and 3 and modeling of the NS5B-dasabuvir complex by the in silico approach. Infect Ecol Epidemiol, 8(1):1528117. doi: 10.1080/20008686.2018.1528117.

Palanisamy N*, Kalaghatgi P, Akaberi D, Lundkvist Å, Chen ZW, Hu P and Lennerstrand J, 2018. Worldwide prevalence of baseline resistance-associated polymorphisms and resistance mutations in HCV against current direct-acting antivirals. Antivir Ther, Epub 10 May 2018. doi:10.3851/IMP3237. *also the corresponding author

Palanisamy N*, Akaberi D, Lennerstrand J and Lundkvist Å, 2018. Comparative genome analysis of Alkhumra hemorrhagic fever virus with Kyasanur forest disease and tick-borne encephalitis viruses by the in silico approach. Pathog Glob Health, Epub 10 May 2018. doi:10.1080/20477724.2018.1471187. *also the corresponding author

Melzer AM and Palanisamy N*, 2018. Deleterious single nucleotide polymorphisms of protein kinase R identified by the computational approach. Mol Immunol, 101:65-73. doi:10.1016/j.molimm.2018.05.026. *corresponding author

Palanisamy N*, Akaberi D and Lennerstrand J, 2018. Protein backbone flexibility pattern is evolutionarily conserved in the Flaviviridae family: a case of NS3 protease in Flavivirus and Hepacivirus. Mol Phylogenet Evol, 118:58-63. doi: 10.1016/j.ympev.2017.09.015. *also the corresponding author

Palanisamy N* and Lennerstrand J, 2018. Biophysical studies on HCV 1a NS3/4A protease and its catalytic triad in wild type and mutants by the in silico approach. Interdiscip Sci, 10(1):143-156. doi: 10.1007/s12539-016-0177-4. *also the corresponding author

Palanisamy N, 2018. Identification of putative drug targets and annotation of unknown proteins in Tropheryma whipplei. Comput Biol Chem,76:130-138. doi: 10.1016/j.compbiolchem.2018.05.024.

Xu HT, Colby-Germinario SP, Hassounah SA, Fogarty C, Osman N, Palanisamy N, Han Y, Oliveira M, Quan Y and Wainberg MA, 2017. Evaluation of Sofosbuvir (β-D-2′-deoxy-2′-α-fluoro-2′-β-C-methyluridine) as an inhibitor of Dengue virus replication. Sci Rep, 7(1):6345. doi: 10.1038/s41598-01706612-2.

Palanisamy N* and Lennerstrand J, 2017. Computational prediction of Usutu virus E protein B-cell and T-cell epitopes for potential vaccine development. Scand J Immunol, 85(5):350-364. doi:10.1111/sji.12544. *also the corresponding author

Palanisamy N*, Osman N, Ohnona F, Xu HT, Brenner B, Mesplède T and Wainberg MA, 2017. Does antiretroviral treatment change HIV-1 codon usage patterns in its genes: a preliminary bioinformatics study. AIDS Res Ther, 14:2. doi: 10.1186/s12981-016-0130-y. *also the corresponding author

Kokkula C, Palanisamy N*, Ericstam M and Lennerstrand J, 2016. SYBR green II dye-based real-time assay for measuring inhibitor activity against HIV-1 reverse transcriptase. Mol Biotechnol, 58(10):619-625. doi: 10.1007/s12033-016-9961-y. *equal first authors

Lindström I, Kjellin M, Palanisamy N, Bondeson K, Wesslén L, Lannergard A and Lennerstrand J, 2015. Prevalence of polymorphisms with significant resistance to NS5A inhibitors in treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden. Infect Dis (Lond), 47(8): 555-562. doi: 10.3109/23744235.2015.1028097.

Eckert N, Wrensch F, Gärtner S, Palanisamy N, Goedecke U, Jäger N, Pöhlmann S and Winkler M, 2014. Influenza A virus encoding secreted Gaussia luciferase as useful tool to analyze viral replication and its inhibition by antiviral compounds and cellular proteins. PLoS One,9(5):e97695. doi: 10.1371/journal.pone.0097695.

Danielsson A, Palanisamy N, Golbob S, Yin H, Blomberg J, Hedlund J, Sylvan S and Lennerstrand J, 2014. Transmission of hepatitis C virus among intravenous drug users in the Uppsala region of Sweden. Infect Ecol Epidemiol, 4:22251. doi: 10.3402/iee.v4.22251.

Palanisamy N, Danielsson A, Kokkula C, Yin H, Bondeson K, Wesslén L, Duberg AS and Lennerstrand J, 2013. Implications of baseline polymorphisms for potential resistance to NS3 protease inhibitors in Hepatitis C virus genotypes 1a, 2b and 3a. Antiviral Res, 99(1):12-7. doi: 10.1016/j.antiviral.2013.04.018.

2010 Bachelor of Technology (B.Tech.) in Biotechnology, Vellore Institute of Technology (VIT) University, Vellore, India

2013 Master of Medical Science (M.MedSc.) in Infection Biology, Uppsala University, Uppsala, Sweden

2014 Master of Science (M.Sc.) in Molecular Biology, International Max Planck Research School, University of Goettingen, Goettingen, Germany

2020 Doctor of Science (Ph.D.) in Biosciences, University of Heidelberg, Heidelberg, Germany