Kumaran Nagarajan

PhD Student

Helmholtz Centre for Environmental Research - UFZ
Department of Proteomics
Permoserstr. 15
04318 Leipzig

Phone 49 341 235 1823
Fax 49 341 235 1786

kumaran

Project Description

Quantitative Assessment of Proteome and Metabolome concerned with Obesity:

As a part of an multidisciplinary project LIFE („Leipziger Interdisziplinärer Forschungskomplex zu molekularen Ursachen umwelt- und lebensstilassoziierter Erkrankungen“) which investigates the effects of lifestyle, environment, genetic and molecular factors on various civilization diseases, I focus on obesity to unravel the disease mechanism and to establish biomarkers for better diagnosis. The adipocytokines which is a major class of proteins regulated in obese individuals and the metabolites involved should be measured by an absolute quantitative method to identify the biomarkers and to correlate these markers with the disease process. This is done by using MRM (Multiple Reaction Monitoring) which provides highly specific and selective quantification


PPD adduct formation with NAT protein:

Para- Phenylenediamine (1,4-diaminobenzene) (PPD), an arylamine, is one of the most common allergens among patients with allergic contact dermatitis. PPD is the most widely used primary intermediate in hair dye formulations. The molecular mechanism behind the recognition of PPD by the immune system has not been fully elucidated.

Although a variety of factors including skin penetration, cellstress, cytotoxicity, and dendritic and T-cell activation determine the sensitizing potential of low molecular weight chemicals such as PPD, the formation of a protein adduct is the primary chemical factor required to initiate the response. Subsequent uptake and processing of modified protein by antigen presenting cells results in immune priming and programming. The electrophilicity and therefore protein reactivity of a chemical is thought to relate closely to its ability to promote an immune reaction. Despite this, little is known about the nature of compound-specific protein modifications and how this relates to the initiation of an immune response. Therefore, an understanding of the links between bioactivation, detoxification, and covalent binding is essential to assess the potential of PPD for an immunological response. It is possible that sensitizing potential relates to a compound’s chemical reactivity toward a few critical amino acids

It was hypothesized that N-Acetyl transferase (NAT) enzymes which can catalyse the transfer of an acetyl group from the thio ester of Acetyl-CoA to a variety arylamines,arylhydroxamines and hydrazines are involved in the initiation of immune response by acting as an hapten carrier by binding with PPD in their catalytic active site-Cys 68. To prove this we are trying to identify the modifications caused by PPD in NAT enzymes by mass spectrometric approaches. Furthermore the kinetics of the modification reaction can also be elucidated.

Methods

• Gel electrophoresis
• MALDI TOF/TOF
• LC-MS/MS
• Q Trap

Co-operation

Prof. Dr. rer. nat. Brunhilde Blömeke.
Department of Environmental Toxicology
Fachbereich VI
Universität Trier
Am Wissenschaftspark 25 - 27, Petrisberg
54296 Trier

Curriculum vitae

Since May 2010



October 2009-April 2010




Jan 2009-May 2009






June 2007-May 2009






July 2004- April 2007

Ph.D student in the Department of Proteomic at the Centre for Environmental Research – UFZ.


Guest sceintist in the Department of Proteomic at the Centre for Environmental Research – UFZ.



Master's thesis in the Department of Biological & Chemical Sciences at the Tata Institute Of Fundamental Research-TIFR, Mumbai,India.Project title:' Engineering and construction of Barstar polyprotein for single molecule AFM studies'.


MSc in Environmental Biotechnology in the Department of Environmental Biotechnology,Bharathidasan University,Tiruchirappalli, India.




BSc in Biotechnology, Pondicherry University,Pondicherry,India.