Dr Jagroop Pandhal
BSc (Hons), MSc (Hons), PhD
I have primarily worked with environmentally sourced samples from a microbiological and molecular biology perspective. After gaining experience in molecular ecology through employment at Sheffield Molecular Genetics Facility I aimed to combine my interests in environmental research with potential applications to issues relevant to societies challenges, and undertook a Masters in Research in Applied Biosciences.
During my doctoral studies I worked at the interface of life sciences and engineering developing quantitative proteomics tools to complement environment-focused projects with functional characterisation. I became interested in proteomics as proteins are the functional entities in cells, driving biological processes. Therefore the proteome provides a window into environmental adaptation mechanisms. The discovery of a potentially novel bacterial clade with a unique combination of tolerance strategies led to the work being featured in an editorial special of Proteomics journal with a podcast interview and I received the Thring Prize for best thesis 2008.
As a Post Doctoral Research Associate, the BBSRC Bioprocess Research Industry Club funded me where I used proteomics as a tool in conjunction with inverse and traditional metabolic engineering techniques, to produce human therapeutic proteins. More specifically this involved characterisation and quantitation of protein post-translational modifications in bacterial cells. Although the aim of this research is bioprocessing, the key element is the development of -omics technologies, building on previous expertise with added complexity of glycosylating components. During this time I lectured in biotechnology, bioprocessing and bioengineering.
New research perspectives are in the field of metaproteomics, the study of proteins in complex environmental samples. Natural biological systems comprise complex combinations of organisms. It is commonly predicted that far less than 1% of microorganisms have been cultured in the laboratory, leaving a wealth of biological knowledge and biotechnological potential untouched and potential distortion of our understanding of microbial functions and adaptations. Moreover, microorganisms commonly function in communities where they interact with each other through exchange of metabolites, genes and cell-cell interactions. Therefore metaproteomics can provide a signature of ecosystem function. This information can be combined with traditional ecology data (theory and experiments), which is the aim of my present research as a NERC fellow.
Metabolic engineering of E. coli for therapeutic protein production
Internationally, biopharmaceutical compounds production is valued at over £200 billion. Industry has a choice of platforms for their manufacture, including animal, plant and microbial cells. Microbial production is industrially vital, and ca. 30% of new biopharmaceuticals approved between 2006-10 employed the Escherichia coli platform. The choice of E. coli in industry is based on the wealth of knowledge, genetic amenability, rapid growth rate, inexpensive growth requirements and good recombinant protein yields.
However, limitations of the E. coli toolbox include its inability to produce complex, glycosylated proteins. We are interested in adding complex protein modifying components to this relatively simple cell chassis and thereby increasing the functionality of this host cell platform. We apply the engineering paradigm of measure, model and manipulate to this cell system to improve glycosylation efficiency.
Research at the interface of ecology and engineering
We rely heavily on our environment for resources such as fresh water, energy and food etc. This dependence is increasing as the human population grows rapidly. However, some of the major advances in technology and engineering that have enabled and sustained this population growth have inadvertently caused widespread environmental damage. One particular example is the growth of agriculture to feed the growing population, particularly in expanding urban conurbations. It has resulted in polluted lakes and rivers, reflected in large-scale algal blooms representing a process caused eutrophication. Eutrophication is bad for many reasons – the water quality is poor, smells bad and natural ecosystem structure and function is destroyed. But there may be a hidden opportunity – algae is a potential source of biofuel, fertiliser and animal feed.
Previous and on-going research
My previous project was aimed at developing and applying proteomic tools for understanding adaptation in environmentally significant organisms. This led to the characterisation of the salt stress response of a tentatively new species of cyanobacteria, isolated from a salt lake in the Sahara.
In addition, I examined the highly abundant and relatively newly discovered marine cyanobacterium, Prochlorococcus. I subsequently used these tools to increase the toolbox of E. coli as a recombinant protein production host.
Recent events, ChELSI opening 2011
Explaining the Movember ‘tache to Richard Dawkins
It is widely recognised that the fundamental training of a biologist and an engineer is different. Mathematical theories and quantitative methods are at the forefront of engineering approaches, and therefore their application to complex systems, including biological, is a useful attribute.
However, biologists have the advantage of formulating better testable hypotheses, experimental designs and data interpretation from these complex biological systems. This is namely due to different techniques and strategies used by life scientists to qualitatively decipher complex systems.
The skills of an engineer and life scientist are therefore complementary. I work at this interface to reveal information about complex biological systems.
Woodruff LB, Pandhal J, Ow SY, Karimpour-Fard A, Weiss SJ, Wright PC, Gill RT. (2013) Genome-scale identification and characterization of ethanol tolerance genes in Escherichia coli. Metabolic Engineering 15:124-33.
Longworth J, Noirel J, Pandhal J, Wright PC, Vaidyanathan S. HILIC- and SCX-based quantitative proteomics of Chlamydomonas reinhardtii during nitrogen starvation induced lipid and carbohydrate accumulation. Journal of Proteome Research 11(12): 5959-71.
Evans C., Noirel J., Ow S.Y., Salim M., Pereira-Medrano AG., Pham T.K., Couto N., Pandhal J., Zou X., Karunakaran E., Biggs C.A., Wright P.C. (2012) An insight into iTRAQ: Where do we stand now? Analytical and Bioanalytical Chemistry Epub ahead of print.
Pandhal J., Desai P., Walpole C., Doroudi L., Malyshev D., Wright PC. (2012) Systematic metabolic engineering for improvement of glycosylation efficiency in Escherichia coli. Biochemical and Biophysical Research Communications 419(3):472-476
Pandhal J., Ow S.Y., Noirel J., Wright P.C. (2011) Improving N-glycosylation efficiency in E. coli using high-throughput proteomics, metabolic network analysis and selective reaction monitoring. Biotechnology and Bioengineering 108(4):902-912.
Noirel J., Evans C., Salim M., Mukherjee J., Ow S.Y., Pandhal J., Pham K., Biggs C.A., Wright P.C. (2011) Methods in quantitative proteomics: Setting iTRAQ on the right track. Current Proteomics 8(1):17-30.
Pandhal J., Wright P.C. (2010) N-Linked glycoengineering for human therapeutic proteins in bacteria. Biotechnology letters 32(9):1189-1198.
Robert F.O., Pandhal, J., Wright P.C. (2010) Exploiting cyanobacterial p450 pathways. Current Opinion in Microbiology 13(3):301-306.
Pandhal J., Noirel J., Wright P.C., Biggs C.A. (2009) A systems biology approach to investigate the response of Synechocystis sp. PCC6803 to a high salt environment. Saline Systems, 7;5:8.
Pandhal J., Ow S.Y., Wright P.C., Biggs C.A. (2009) Comparative proteomics study of salt tolerance between a nonsequenced extremely halotolerant cyanobacterium and its mildly halotolerant relative using in vivo metabolic labeling and in vitro isobaric labelling. Journal of Proteome Research, (2):818-28.
Pandhal J., Snijders A.P., Wright P.C., Biggs C.A. (2008) A cross-species quantitative proteomic study of salt adaptation in a halotolerant environmental isolate using 15N metabolic labelling. Proteomics (11):2266-84.
Pandhal J., Wright P.C., Biggs C.A. (2008) Proteomics with a pinch of salt: A cyanobacterial perspective. Saline Systems, 4:1.
Pandhal, J., Wright, P.C., and Biggs, C.A. (2007) A Quantitative Proteomic Analysis of Light Adaptation in a Globally Significant Marine Cyanobacterium Prochlorococcus marinus MED4. Journal of Proteome Research, 6, 3, 996 – 1005.
Tingay, R..E. Dawson, D.A., Pandhal, J., Clarke, M., David, V., Hailer, F., Culver, M., (2007) Isolation of 22 new Haliaeetus microsatellite loci and their characterization in the critically endangered Madagascar fish-eagle (Haliaeetus vociferoides) and three other Haliaeetus eagle species. Molecular Ecology Notes, 7 (5), 711-715.
Struebig, M.G., Horsburgh, G.J., Pandhal, J., Triggs, A, Zubaid, A., Kingston, T., Dawson, D.A, Rossiter, S.J. (2007) Isolation and characterisation of microsatellite loci in the papillose woolly bat, Kerivoula papillosa (Chiroptera: Vespertilionidae). Conservation Genetics, (10.1007/s10592-007-9384-1).
Dawson, D.A., Burke, T., Hansson, B., Pandhal, J., Hale, M.C., Hinten, G.N., Slate, J. (2006) A predicted microsatellite map of the passerine genome based on chicken-passerine sequence similarity. Molecular Ecology, 15 (5), 1299-320.
Berg, P.R., Dawson, D.A., Pandhal. J., Kirkendall, L.R., Burke, T. (2003) Isolation and characterisation of microsatellite loci from two inbreeding bark beetles (Coccotrypes). Molecular Ecology Notes, 3 (2), 270-273.