E-mail: kangueane{at}bioinformation.net

E-mail: kangueane{at}gmail.com

October 16, 2017

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Research Experience

Research Interest

Research Experience (1994-2017)

(Honesty, Hard Work and Perseverance)

Current Research

Short peptide vaccine design

Short antigen peptides capable of binding host HLA molecules can be used to design peptide vaccines by exploiting T-cell immunity. Two problems with the design of such a cocktail vaccine are antigen peptide diversity from viral/bacterial proteome and host HLA allele polymorphism. In 2002, we (P. Kangueane, M.K. Sakharkar, E.C. Ren and P.R. Kolatkar) developed a method to predict peptides binding to HLA molecules using side chain packing molecular modeling techniques developed by S. Subbiah (Kangueane et al. 2000). It should be noted that S. Subbiah made several generous contributions towards this study. We (E.C. Ren, P. Kangueane and P.R. Kolatkar) also studied the binding of mHag (minor histo-compatibility antigen involved in graft versus host disease) peptides to HLA A alleles (Ren et al. 2000). Betty Cheng gave her ORIGIN SGI machine to perform the modeling calculation and data storage. In 2001, we (P. Kangueane, M.K. Sakharkar, E.C. Ren and P.R. Kolatkar) studied the structural principles of HLA-peptide binding using a dataset of HLA-peptide crystal structures (Kangueane et al. 2001). Later, Adrian helped us study the type of inter-atomic interactions at the interfaces of HLA-peptide structures using a dataset (Adrian et al. 2002). In 2002, T.W. Tan, R. Shoba and their student Govindarajan helped me develop the MIDB database in 2003 (Govindarajan et al., 2003). In 2003, Bing Zhao helped us develop methods to compress functional diversity among HLA alleles (Zhao et al. 2003a) and to predict HLA-peptide binding (Zhao et al. 2003b). This later helped us (P. Kangueane, P. Shapshap, S. Subbiah) to subtype HLA super-types (functional overlap among alleles) in 2005 (Kangueane et al. 2005). We then demonstrated the utility of this technology in the design of a gp120 peptide vaccine cocktail vaccine for NeuroAIDS in a book chapter edited by Karl Goodkin (Kangueane et al. 2008). This work was done at National University of Singapore and NANYANG Technological University, Singapore. Mohana Priya, a Senior Assistant Professor at VITU, India comlpleted class 2 HLA-peptide binding prediction using structural principles (Mohanapriya, 2009; 2010; 2007-2010; 2017).

Protein-protein interaction

During the summer of 1995, I had an opportunity to work on the principles of protein-protein interaction at the labs of P. Balaram and C. Ramakrishnan using a dataset of protein structural complexes. I started working with K. Gunasekaran to understand protein subunit principles at the Molecular Biophysics Unit, Indian Institute of Science. Since then until 2002, I was not able to revisit the protein subunit interaction problem. It was in 2002, Li Lei (graduate students at the NANYANG Technological University) and Cui Zhanhua (graduate students at the NANYANG Technological University) showed interest to study protein-protein interaction under my advice. Li Lei helped to study LIGAND effect at the homo-dimer interface (Li et al. 2005) and homo-dimer folding (Li et al. 2005). Cui Zhanhua helped to identify critical interaction parameters at the hetero-dimer interface (Zhanhua et al. 2005) and differentiated hetero-dimer from homo-dimer interfaces (Zhanhua et al. 2005). The initial part of this work was done at the Molecular Biophysics Unit, IISC, India (1995) and later part was done at NTU, Singapore (2002-2006). Sajitha Lulu, a graduate student at VITU, India is looking at the principles of homo-dimer folding and binding using structural data (Lulu et al. 2009; 2007-2008). This project is also participated by V. Karthikraja (2009); A. Suresh (2009-2010); G. Sowmya (2009-2010) and G. Shamini (2009-2010). The role played by Christina Nilofer in 2017 is highly commented.

Past Research

Lipase engineering

During the summer of 1996, I started working with P. Gautam and B.S. Lakshmi on several aspects of lipase engineering. We (P. Kangueane, P. Gautam, B.S. Lakshmi and B. Abraham) optimized lipase production by Candida rugosa using vegetable oils as substrates (Lakshmi et al. 1999). Later, we (P. Kangueane, P. Gautam, B.S. Lakshmi, Y. Gao and Y.Z. Chen) showed the stereo-specificity of S(+) ibuprofen to Candida rugosa (Lakshmi et al. 2000). We (P. Kangueane, P. Gautam, B.S. Lakshmi and M. Krishnan) also developed a simple, fast, sensitive assay method for Candida rugosa lipase using a bi-phasic reaction system (Lakshmi et al. 2000). In 2003, James and colleagues (B.S. Lakshmi, P. Gautam, P. Kangueane) showed the flap movement in different pH conditions using molecular dynamics simulation (James et al. 2003). I really enjoyed most of my work/association with lipase engineering and it was full of fun. This work was done at the Centre for Biotechnology, Anna University during 1996-2003 in close association with P. Gautam and B.S. Lakshmi.

Exon-Intron analysis

It was a great pleasure to work with K. S. Meena during 1999-2000 on the development of IEKB (Intron-Exon knowledge base) using ExInt and GenBank (Sakharkar et al. 2000). We continued to work on SEGE (single exon genes in eukaryotes) during 2001-2002 (Sakharkar et al. 2002). Later, we developed Genome SEGE and examined their features in 2004 (Sakharkar et al., 2004a; Sakharkar et al. 2004b; Sakharkar et al. 2005). Nidhi Dhandona, Iti Chadurvedi and Kingshuk Gosh made contributions among many others towards this project. In 2003, we (P. Kangueane & M. K. Sakharkar) recruited Lee Pern Chern, Xue Hao and Bhagavati Perumal to look into many other issues of introns in eukaryotes. This let to the continued maintenance of ExInt (Sakharkar et al., 2005d), development of human alternative splicing database (Sakharkar et al. 2004), a study on introns in tubulins (Bhagavati et al. 2005) and gene patterns by exon-intron combinations in the human genome (Sakharkar et al. 2005a). In this connection, we found that in both human and mouse genomes, the total length in introns and intergenic DNA on each chromosome is significantly correlated to the chromosome size (Sakharkar et al. 2004; Sakharkar et al. 2005). These findings have implications in chromosome design in eukaryotes. We also further developed the U-genome database containing information on exon-intron-exon in unicellular eukaryotic genomes (Sakharkar et al. 2005).

Gene fusion

Gene fusion is a phenomenon that has generated much curiosity since its description. Human fusion proteins are found to mimic operons and protein-protein interfaces in prokaryotes. They are also found to exhibit multiple functions and alternative splicing. We provided a comprehensive list of fusion proteins of prokaryotic origin in the human genome (Yu et al. 2004). We also suggested that fusion gene products and their evolution have had a key role in the selection of complex multifaceted networks (Sakharkar et al. 2005). The evolutionary force for gene fusion is illustrated using molecular dynamics simulation of IGPS (Yiting et al. 2006).

Cry toxin from Bacillus thuriengis

During the summer of 1994, after a small stint with the research and development section (yeast and tablet formulation) at TTK Pharma (Pallavaram Branch), India, I started working on Bacillus thuriengis (B.t). We (P. Kangueane, G. Kalaiselvi and R. Sachidanandam) were trying to estimate the individual population dynamics of B.t.a (Bacillus thuriengis subspecies aizawai) and B.t.k (Bacillus thuriengis subspecies kurstaki) in a co-culture system. The reason to co-cultivate B.t.a and B.t.k is to develop a combined formulation for endo-toxins produced by these two sub-species of B.t (for better pesticide activity). Similar morphology between B.t.a and B.t.k gave us hard time, determining the individual species dynamics in a co-culture system. The results were interesting and encouraging. However, after spending 18 months (I hardly closed my eyes during this time) on the project, working through the night, we were not able to publish the results due to logistics. This work was done at the International center for bioprocess technology, Anna University. Some industrial trainees (we lost Mr. Manivannan to brain fever during a field study and the news was shocking) from TUTICORIN Alkali Chemicals also played an active role in this work during 1994-1995.

Signed by

Dr. P. Kangueane

Chief Editor, Bioinformation

Professor of Biotechnology and Bioinformatics