Tej P Singh

Professor Tej P. Singh is an eminent Indian scientist who has made original and novel contributions to the structural studies of proteins and has implemented a strong programme on structure - based rational drug design.

Work

The three-dimensional structures of various proteins including lactoferrin from several species, ribosome inactivating protein and its complex with a natural ligand from mistletoe, bifunctional inhibitor proteins from plant seeds and various serine proteases and their inhibitors have been determined by him.

The elaborate structural studies of proteins from several important systems as potential drug targets such as phospholipase A2, cyclooxygenase, lipoxygenase, endothelin receptor, endothelin converting enzyme, breast cancer regression proteins and matrix metanosomal proteins as well as their complexes with natural and designed synthetic ligands have been carried out.

His laboratory has submitted more than 243 sets of proteins structure coordinates in the protein data bank (PDB) which makes it the highest number in India. Initially, he had contributed significantly on the structure - function studies of a number of antipyretic, analgesic and anti-inflammatory agents and then on antibactrial sufonamides and their derivatives. He had developed the rules of peptide design with alpha, beta – dehydro - amino acids through extensive studies using syntheses, and X-ray and NMR structure determinations. These design rules are being exploited for making specific peptides to act as tight inhibitors of target enzymes and potent antagonists of target receptors for eventually leading to useful therapeutic agents.

As part of his protein structural studies, a large number of structures of lactoferrin proteins from various species in iron-saturated and apo-forms as well as those of its proteolytically generated monoferric functional N- and C-lobes have been determined in his laboratory through which it was demonstrated that large scale conformational changes occur in the structures of lactoferrins upon iron-binding and iron-release, cations other than ferric ion also bind to the iron-binding cleft but with lower affinity, similarly anions other than carbonate/bicarbonate can also bind with reduced potency, and bilobal lactoferrin can be converted into two functional N-terminal and C-terminal lobes with proteinase K. It was only his group in the whole world that successfully demonstrated the proteolytic production of N- and C-terminal molecular halves of lactoferrin and determined their three-dimensional structures. These studies have provided valuable insights into the structural basis of iron-binding and iron-release in lactoferrins and their roles as antibacterial agents and in other therapeutic applications.

While carrying out enzymatic cleavage of lactoferrin proteins, a novel antifungal decapeptide was discovered whose excellent potency against bacterial infections has been established.

His group has carried out extensive structural studies of phospholipase A2 enzymes and their complexes with various natural compounds, substrate analogues, non-steroidal anti-inflammatory agents and designed peptides. The new molecules have also been designed against cyclooxygenase and lypoxygenase. The enzymes phospholipase A2, cyclooxygenase and lypoxygenase are involved in the production of pro-inflammatory compounds collectively called as eicosanoids. He has already developed several highly potent inhibitors that are under consideration for further evaluation as anti-inflammatory agents. His group has been practicing the rational approach of structure-based drug design for developing therapeutic agents against various inflammatory disorders such as rheumatism and arthritis using PLA2, COX-2 and LOX enzymes as macromolecular targets.

In yet another area of current interest, his group has determined the crystal structures of several secretory glycoproteins isolated from dry secretions of various mammalian species including humans. This is a new class of proteins, first time detected whose functions and structures were unknown. These proteins are implicated as protective signaling factors in the large scale tissue remodeling processes. Their role in the breast cancers as protective factors for the breast cancer cells makes them important targets for structure - based drug design and offers opportunities for developing new therapeutic agents against breast cancer. He has been able to design several peptides that bind to these proteins with potencies ranging up to 10-7 M. The crystal structures of the complexes of these proteins with designed peptides have helped in identifying the site of binding in this protein. The structures of the complexes with various oligosachharides have provided information about the potencies of sugar binding. It also indicated the type and nature of sugars that will bind to this class of proteins specifically. Furthermore, several crystal structures of the ternary complexes of these proteins with peptides and sugars have helped in understanding the mode of binding of these proteins to cell surface receptors.

Recently he initiated a new programme on Clinical Proteomics in which it is intended to characterize all the proteins that are expressed during various patho/physiological conditions. The newly identified proteins will either be useful as biomarkers or they may be associated with the progression of diseases making them important targets for drug design.

He has published more than 260 research papers in the leading journals.

Education

Professor Tej Singh obtained his Masters in Science in first rank from the University of Allahabad. He started his research career in 1971 as a graduate student at the Indian Institute of Science, Bangalore. He obtained his Ph. D degree in the mid 70's working on the crystal structure determinations and design of anti-inflammatory analgesics for new drug discovery.

Area of Specialization

Structural Biology ; Protein Crystallography ; Rational Structure based Drug Design and Drug Discovery

Professional career

Soon after obtaining his Ph. D degree, he worked about a year (1977) as a lecturer at the University of Indore. He then spent more than two years (1978-1980) as an Alexander von Humboldt / Max-Planck, post doctoral fellow in the German laboratory of Professor Robert Huber, who later received the Nobel Prize. After his return to India he worked as a reader at Sardar Patel University (1980-83) and an Additional Professor (1984-85) in the Department of Biophysics at the All India Institute of Medical Sciences, New Delhi. He was appointed Professor and Head of the Department in 1986, where he established a flourishing school of structural biology and new drug discovery.

Awards and Honors

GN Ramachandran Gold Medal for excellence in Science and Technology (CSIR), 2006

Distinguished Biotechnologist (DBT), 2006

Vice President, Indian National Science Academy, 2007-2009

JC Bose Memorial Award, 2005

Alexander von Humboldt Fellow, 1977

Canadian Development Agency Award, 1999

Fellow of the Indian Academy of Sciences, 1994

Fellow of the National Academy of Sciences, 1998

Fellow of the Indian National Science Academy, 2000 -

Fellow of the Third World Academy of Sciences : F.T.W.A.S. 2003 -

Member of the Commission on Biological Macromolecules of the International Union of Crystallography (IUCr) (2005 - 2008)

Executive member of the International Union of Pure and Applied Biophysics (IUPAB) (2002-2005)

Member Secretary of the INSA National Committee for IUPAB (1988 - 91)

Member of the INSA National Committee for International Union of Pure and Applied Biophysics (IUPAB) (1985 - 88)

Member of the INSA National Committee for International Union of Crystallography (IUCr) (2000 - 2003)

Ex-officio member of the Joint National Committee of INSA for IUPAB and IUCr (2002 - 2005) , (2005 - 2008)

Member of a committee to select fellows for Indian National Science Academy (2001 - 2003)

Member of the Committee to select fellows for the Indian Academy of Sciences, 2005

Member of the Indian Biophysical Society since 1977

Member of the Society of Biological Chemists of India , 1982

Vice President of the Indian Biophysical society (1994 - 1996)

Member of the American Society for Biochemistry and Molecular Biology (ASBMB), since 2000

Member Technology Development Board on Pharmaceutical Industry (2002)

Member of the Senate of Indian Institute of Technology Delhi, (2001 - 2002)

Chairman of the DST Committee for the Fast Track Programme in life Sciences (2002 - 2004) , (2005 - 2007)

Member of the Apex Committee of the DBT for the programme support at I.I.Sc. Bangalore (1998 - 2001), (2002 - 2004) , (2005 - 2008)

Member of the Programme Advisory Committee of DST on Biochemistry, Biophysics, Molecular Biology including Microbiology (1996 - 1998) , (1999 - 2001)

Member of the DBT task force on Basic Biology / Modern Biology (1996 - 1998) , (1999 - 2001)

Member of the DBT task force on Infrastructure (2001-2003) , (2004 - 2006) , (2006 – 2008)

Member of the DBT task force on Bioinformatics (1994 - 1996)

Member of the Advisory Committee of Biotechnology Teaching Programme of the Biotechnology Centre, JNU (2002)

Member of the Executive Committee of the Bioinformatics Centre at Madurai Kamraj University (2002 - 2003)

Member of the Academic Committee of the Biotechnology Unit of AMU, Aligarh (2004 - 2006)

Member of the Research Area Panel of the National Institute of Immunology (1994 - 1996)

Member of the Special Committee of the School of Life Sciences, JNU (1988 - 1990) , (1991 - 1993)

Member of the Special Committee of the Centre for Biotechnology, JNU (1991 - 1993) , (1994 - 1996) , (1997 - 1999) , (2000 - 2002) , (2003 - 2005)

Member of the Special Committee of the Special Centre of Molecular Medicine, JNU (2001 - 2003) , (2004 - 2006)

Member of the Special Committee of the School of Environmental Sciences, JNU (2001-2003) , (2004 - 2006)

Member of the Academic Committee of the Nuclear Science Centre, New Delhi, (2002 - 2004), (2004 - 2006)

Member of the Academic Committee of Central Drug Research Institute, Lucknow, (2005 - 2006)

Member of the Academic Committee of the Institute of Microbial Technology, Chandigarh, (2005 - 2006)

Member of the Executive Council of the Centre of Bioinformatics, Institute of Microbial Technology, Chandigarh, 2005

Member of the Academic Council of the Central Unversityof Hyderabad, 2006 - 2007

Executive member of the Council of the International Union of Pure and Applied Biophysics (IUPAB) (2005 - 2008)

K.K.Foundation National Award for Science and Technology, 2001

Chairman of the Fast-Track Programme of DST in Life Sciences, 2001 – 2003

Member of the Technology Development Board on Pharmaceutical Industry, 2002 - 2003

Executive member of the Council of International Union of Pure and Applied Biophysics, 2002 – 2005

Max-Planck - Humbodt Award - 1999

Canadian Development Agency Award - 1991

Danish International Development Agency Award - 1978

First Rank in M.Sc. in the University of Allahabad - 1971

External links

* http://dst.gov.in/whats_new/press-release07/biotech-award.htm
* http://www.jbc.org/cgi/reprint/M208967200v1.pdf
* http://timesofindia.indiatimes.com/articleshow/753224.cms
* http://www.bio-medicine.org/medicine-news/Five-New-Anti-Inflammatory-Compounds-Produced-By-Indian-Scientists-6838-1/
* http://pib.nic.in/release/release.asp?relid=25773