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Structural bilogist-protein expression,purification&structure solution

Location:
Birmingham, AL, 35216
Salary:
$50,000 per annum
Posted:
January 24, 2012

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Resume:

Baskar Raj Savarimuthu, M.Sc. Ph.D.

****-*, ******** **** **. Birmingham, AL 35216

Phone : 205-***-**** E-mail: hpbw2d@r.postjobfree.com

PROFILE

Hard working and resourceful with excellent communication and interpersonal skills.

Excellent analytical and quantitative abilities in team building, organization and strategic planning.

Fast learner and adaptable to changes and works well with people of different cultures.

AREAS OF EXPERTISE

Structural Chemistry:

X-ray Crystallography

Supramolecular Chemistry and Crystal Engineering

Structure-based Drug Design

Structural Biology:

Crystallization of proteins, RNA and its complexes (PHOENIX Art Robbins)

Data collection and processing (d*TREK, Denzo, Scalepack)

structure determination (CCP4, Phenix)

structure refinement, model building and structure visualization and analysis (Refmac, coot, O, Pymol)

Molecular biology:

Cloning

Protein expression and purification (AKTA-FPLC)

DNA isolation and RNA purification (Electrophoresis)

Molecular modeling:

Structure visualization, modeling and analysis (Maestro, Impact, Glide)

Brief description of the current work at Southern Research Institute, Birmingham

Structure and Function of Proline-rich Tyrosine Kinase (Pyk2): Pyk2 is a non-receptor tyrosine kinase (PTKs) implicated in integrin-dependent tyrosine-phosphorylation and engage in focal adhesion where it colocalizes with several other proteins to transduce information from cells to the extracellular matrix and vice versa. Increased expression of Pyk2 has been observed in several human tumors.

Our goal in studying the structure of this enzyme is

to reveal the functional role that Pyk2 plays in cellular biology and

to manipulate this kinase enzyme as a potential molecular therapeutic target for cancer.

Pyk2 composed of number of functional domains including the NH2-terminal FERM domain, a central catalytic kinase domain and a carboxyl-terminal focal adhesion targeting (FAT) domain.

To achieve our goal

Data were collected to 3.2Å from a crystal of Pyk2 Ferm domain and the manuscript is in preparation.

In pursuit of studying the full length Pyk2 structure, recently we collected several data sets ranging from 1.7 – 2.0Å from crystals containing Ferm and kinase domains of Pyk2. Structure determination is in progress

Summary of the work done at Department of Chemistry, University of Louisville

Study on the structure and function of self-aminoacylating ribonucleic acids (RNA) using x-ray crystallography: RNA can act as biocatalysts and should, in principle, be able to catalyze most biological reactions currently catalyzed by proteins. Our aim in studying the structure of RNA was

To unravel the functions of a catalytic RNA at the atomic level

To understand how ribozymes (RNA) recognize substrates and perform catalytic functions

How can we modify these functions through structure-based RNA design

To address these, I had crystallized and optimized growth conditions in two different crystal lattices of a particular RNA that has 66 nucleotides. The crystallographic data has been collected both on a diffractometer (a rotating anode x-ray source) as well as at the synchrotron facility (Advanced Photon Source-Argonne National Lab., Chicago).

Summary of the work done at Department of Biochemistry, The University of Iowa

Study on high resolution structures of Alcohol Dehydrogenases (ADH): ADH plays an important physiological function in Mammals, where it facilitates the reversible oxidation of alcohols into aldehydes and ketones with Nicotinamide Adenine Dinucleotide (NAD) as the coenzyme. In yeast and bacteria, ADH plays a similar role in fermentation, where it catalyzes acetaldehyde into ethanol. These structural studies of ADHs are important in developing therapeutic drugs for acute alcoholism and drug dependency in patients.

Towards this effort I had worked on three different projects.

Solved complex structures of Liver Alcohol Dehydrogenase with selected lead compounds that would potentially treat poisoning by methanol and ethylene glycol.

Determined the structures of Liver ADH apo-enzyme and complexes with ligands that bind to the catalytic zinc ion.

Determined the Yeast (Saccharomyces cerevisiae) ADH, the enzyme of choice for the production of ethanol from corn.

Structures Deposited in Protein Data Bank (RCSB)

Horse Liver Alcohol Dehydrogenase Apoenzyme (1YE3)

Yeast Alcohol Dehydrogenase I, Saccharomyces cerevisae fermentative enzyme (2HCY)

Summary of the Research work done at School of Chemistry, Bharathidasan University

Crystallographic Studies of some complexes of Sulphoxine and Trimethoprim: Sulphoxine and Trimethoprim are antiamoebic and antibacterial drugs respectively.

Studied the metal binding modes of sulphoxine.

Studied trimethoprim-carboxylate interactions.

Obtained some remarkable structural motifs, in the form of H-bonded chains, sheets and networks. These motifs are potentially important for molecular recognition in the fields of crystal engineering/supramolecular chemistry. Interestingly, some of the H-bonded interactions discovered in my studies have actually been observed in protein-nucleic acid interactions thereby proving that these interactions could be considered as a model for drug-receptor recognition (the aminopyrimidine moiety of the drug forms H-bonds with the carboxylate anion of the receptor molecule).

EDUCATION

1999 - 2003: Ph.D. Chemistry (X-ray crystallography), Bharathidasan University, India

1996 - 1998: M.Sc. Chemistry, St.Joseph’s College, Tiruchirappalli, India

1993 - 1996: B.Sc. Chemistry, St.Joseph’s College, Tiruchirappalli, India

EMPLOYMENT

2009 – 2011 : Postdoctoral Researcher, Southern Research Institute, Drug Discovery Division, Birmingham, AL.

2006 – 2008 : Postdoctoral Research Fellow, Department of Chemistry, University of Louisville, Louisville, KY.

2004 – 2006 : Postdoctoral Research Fellow, Department of Biochemistry, University

of Iowa, IA.

2002 – 2003 : Senior Research Fellow (Council of Scientific and Industrial Research,

Government of India)

1999 – 2001 : Research Scholar, Bharathidasan University, Tiruchirappalli, India.

THESIS / DISSERTATION

Ph.D. "Crystallographic Studies of some complexes of Sulphoxine and Trimethoprim"

FELLOWSHIPS AND AWARDS

Senior Research Fellowship, Council of Scientific & Industrial Research,

India (CSIR-SRF) From 2002 to 2004 (Ref.No. 9/475(103)/2002-EMR I)

JUDGING POSTERS

Research Louisville 2007, University of Louisville, Louisville, October 16-19, 2007

PUBLICATIONS

1. Baskar Raj S, Stanley N, Thomas Muthiah P, Bocelli G, Ollá R and Cantoni

A. 2003. Crystal engineering of organic salts: Hydrogen-bonded supramolecular

motifs in trimethoprim sorbate dihydrate and trimethoprim o-nitrobenzoate.

Crystal Growth & Design., 3(4), 567-571.

2. Baskar Raj S, Sethuraman V, Francis S, Hemamalini M, Thomas Muthiah P,

Bocelli G, Cantoni A, Rychlewska U and War.zajtis B. 2003.

Supramolecular Organisation via Hydrogen Bonding in Trimethoprim sulphonate salts.

CrystEngComm,. 5(15), 70-76.

3. Baskar Raj S, Thomas Muthiah P, Rychlewska U and War.zajtis B. 2003.

Pseudo-polymorphism and Crystal Engineering: Hydrogen-bonded supramolecular

networks in Trimethoprim m-chlorobenzoate and Trimethoprim m-chlorobenzoate

dihydrate. CrystEngComm, 5(9), 48-53.

4. Baskar Raj S, Thomas Muthiah P, Bocelli G and Cantony A. 2003. Interplay of

coordination and hydrogen bonding modes in the self-assembly of the

supramolecular network in copper(II)-phthalate-trimethoprim complex (0.5:1:1).

Inorganic Chemistry Communications, 6(6), 748-751.

5. Baskar Raj S, Thomas Muthiah P, Rychlewska U, War.zajtis B, Bocelli G and

Olla R. 2003. Interplay of coordination, pi-pi stacking and hydrogen bonding in

the supramolecular self-assembly of bis[triaaqua(7-iodo-8-hydroxyquinoline-5-

sulphonato-N,O,O) nickel(II) dihydrate]. Acta Cryst. E59, m46-m49.

6. Baskar Raj S, Thomas Muthiah P, Bocelli G and Cantoni A. 2003. Bis[(8-

hydroxyquinoline-5-sulfonate)(4,4'-bipyridinium)] 4,4'-bipyridine pentahydrate.

Acta Cryst. E59, o1980- o1983.

7. Baskar Raj S, Thomas Muthiah P, Bocelli G and Olla R. 2002. Metal binding

modes in sulphoxines: supramolecular network in (8-hydroxyquinoline-5- sulphonato-

N1,O8) sodium(I). Acta Cryst. E58, m513-m516.

8. Baskar Raj S, Thomas Muthiah P, Bocelli G and Righi L.2001, Tetraaqua(8-

hydroxyl quinoline -5-sulphonato-N,O) nickel(II) monohydrate. Acta Cryst. E57,

m591- m594.

9. Justin Robert J, Baskar Raj S, and Muthiah P. T., 2001. N-H…O and O-H…O H-

bonds in crystal engineering: Trimethoprim hydrogen glutarate.Acta Cryst. E57,

o1206-o1208.

10.Justin Robert J, Baskar Raj S, Bocelli G, Olla R, and Thomas Muthiah, P. 2001.

Metal-nucleobase interactions:dibromobis(cytosine)cadmium(II). Acta Cryst. E57,

m558-m560.

11.Stanley N , Amaladasan M, and Baskar Raj S. 2001, Asian Journal of Chemistry,

Vol.13, 1109-1113.

MANUSCRIPTS IN PREPARATION

1. Baskar Raj S, Plapp B. V & Ramasamy S. Asymmetry in a Structure of Yeast

Alcohol Dehydrogenase.

2. Baskar Raj S, Rongbao Li & Wang Y. Crystal Structure of Ferm domain of Proline-

rich Tyrosine Kinase2.

SCIENTIFIC PRESENTATIONS AND WORKSHOPS

Wang, Y., Zhai, L., Masters, E., Greenwood, J., Maddox, C., Baskar Savarimuthu, Roy, A.M., Wennerberg, K., White, E.L., Zhang W., Ananthan, S., Qu, Z. and Li, R.(2009) Targeting PYK2 for Brain Tumor Therapeutic Development. XIII Annual UAB Comprehensive Cancer Center Research Retreat, University of Alabama, Birmingham, October 28, 2009.

Baskar Raj S, Ramasamy S & Bryce Plapp(2005) Asymmetry in a Structure of Yeast Alcohol Dehydrogenase. Fourteenth Biocatalysis and Bioprocessing conference on “Biocatalysis – from Specialty to Commodity Chemicals”, The Center for Biocatalysis and Bioprocessing, The University of Iowa, Iowa city, October 24-25, 2005.

Baskar Raj S, Bryce Plapp, Daniel B. Rubenstein & Ramasamy S (2004) Protein Dynamics from X-ray Crystallography. Thirteenth Biocatalysis and Bioprocessing conference on “Environmentally Beneficial Biocatalysis”, The Center for Biocatalysis and Bioprocessing, The University of Iowa, Iowa city, October 25-27, 2004.

Fifth national Symposium in Chemistry (NSC-5), Central Leather Research Institute, Chennai, India, 7-9 February, 2003.

Tenth Workshop on Neutrons as Probes of Condensed Matter (NPCM-X), Solid State Physics Division, BARC, Mumbai & Bhavnagar University, Bhavnagar, India, Feb28-Mar15, 2002.

National Workshop on Molecular Biophysics, Department of Physics, Bharathidasan University, Tiruchirappalli, India, 28-30 March, 2001.

Baskar Raj S & Muthiah PT (2001) Diaminopyrimidine-carboxylate interactions in Trimethoprim complexes. IVth Meeting of Asian Crystallographic Association (AsCA'01), Indian Institute of Science, Bangalore, India, 18-21 November, 2001.

All India Workshop/Training Course on Application of Direct Methods in Crystallography for Small/Medium sized molecules, Department of Biophysics and Crystallography, University of Madras, Chennai, India, 1-21 December, 1998.



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