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Dr. N. Saha

 

FACULTY

Name:  Dr. Nirmalendu Saha, Ph.D, FNASc., FZS

Designation:  Professor of Zoloogy

Specialization:  Biochemical Adaptation and Metabolic Regulation

 

Contact Information:

Biochemical Adaptation Laboratory
Department of Zoology,
North-Eastern Hill University
Shillong 793022, INDIA

Tel.: +91 364 272 2322 (work), +91 364 2550752 (home), +91-9436100836 (mobile)
E-Mail: nsaha@nehu.ac.in, nsahanehu@hotmail.com      

 

Academic Qualifications:

Degree

Year

University

B. Sc.

1980

North-Eastern Hill University, Shillong

M. Sc.

1982

North-Eastern Hill University, Shillong

Ph. D.

1987

North-Eastern Hill University, Shillong

 

Fellowships/Awards/Recognitions:

National:

  • Fellow of National Academy of Sciences, India (F.N.A.Sc.)
  • Fellow of Zoological Society, Kolkata (F.Z.S.)
  • Received the ISCA Young Scientists Award by the Indian Science Congress Association in the year 1990.
  • Received the Young Scientist Best Speaker Prize and a gold medal by the Ichthyological Society of India for the year 1987.
  • Received the National Merit Scholarship from Matriculation up to M.Sc.

International:

  • DAAD Fellow (June 1 1991 to September 1993)
  • Senior DAAD Fellow (October 1 to December 31, 1997)
  • Visiting Scientist (BAT II) on invitation in the laboratory of Professor Dr. D. Häussinger, Germany (May 1, 2001 to April 2002)
  • Senior DAAD Fellow (December 1, 2005 to January 31, 2006)

 

Memberships of academic societies, etc.:

  • Life Member of the National Academy of Sciences, Allahabad, India
  • Life Member of the Indian Science Congress Association, Kolkata
  • Life Member of the Indian Society of Biological Chemists
  • Life Member of the Indian Society of Comparative Animal Physiologists

Major areas of research:

  • Nitrogen metabolism in air-breathing teleosts with special reference to ornithine-urea cycle (OUC) and amino acid metabolism under environmental stresses.
  • Molecular mechanisms of regulation of ureogenesis and amino acid metabolism under environmental constraints in air-breathing catfishes.
  • Nitrogen and carbohydrate metabolism, oxidative stress and protein turnover with relation to cell volume changes in air-breathing catfishes.
  • Cell volume changes and early immediate gene expression in the hepatocytes of air-breathing catfishes.
  • Molecular characterization and regulation of expression of different nitric oxide synthase genes and the role of nitric oxide under environmental stresses in air-breathing teleosts.
  • Oxidative stress and antioxidant properties of air-breathing catfishes under environmental stresses.
  • Influence of nanoparticles on oxidative stress and antioxidant properties in air-breathing catfishes.

 

Most significant research contribution made by Prof. N. Saha and his group:

Prof. Saha and his group has shown for the first time the presence of a functional ornithine-urea (o-u) cycle in some freshwater air-breathing teleosts that are predominantly available in Indian subcontinent, such as Heteropneustes fossilisClarias batrachusAnabas spp. and Monopterus cuchia (Saha and Ratha, 1987, 1989; Saha et al., 1999), which otherwise was known to be non-functional or absent in all freshwater teleosts. This unique finding by Prof. Saha has contradicted the earlier “gene deletion” hypothesis proposed by Brown and Cohen (Biochem. J., 75: 82-91, 1960) based on their findings on non-occurrence of functional o-u cycle in teleosts. According to this hypothesis, some of the genes responsible for synthesis of o-u cycle enzyme proteins got deleted in the process of evolution of teleosts from marine to the freshwater habitat, since the osmotic problem reversed in the freshwater habitat compared to the marine counterpart. Prof. Saha has also shown, as a unique adaptation, that the functional o-u cycle could be stimulated at least in two air-breathing catfishes (C. batrachus and H. fossilis) under various environmental stresses, which they face in their natural habitat,  such as while living inside the mud-peat for months during the drought season (Saha et al., 2001), during exposure to higher ambient ammonia (Saha and Ratha, 1990, 1994; Saha and Das, 1999; Saha et al., 1995, 2003, 2007), and also to alkaline environment (Saha et al., 2002),  thus leading to a switch over from ammoniotelic mode of nitrogen excretion to ureotelic one. This unique adaptation, found generally in amphibians, was not reported earlier in any teleost species. Furthermore, Prof. Saha has also shown the existence of a functional o-u cycle in extra-hepatic tissues such as kidney, intestine and muscle in some of these air-breathing fishes (Saha and Ratha, 1987, 1989; Saha et al., 1999). Prof. Saha has also shown that C. batrachus has the capacity to convert very efficiently the toxic ammonia, generated endogenously or coming from external sources, to glutamine and various non-essential free amino acids (Saha et al., 2000, 2002, 2007) as another physiological strategies to tolerate a very high external ammonia. Thus, due to possessing all these unique biochemical adaptational flexibilities related to nitrogen metabolism, these air-breathing fishes, found mostly in Indian sub-continent, are able to live successfully for months inside the mud-peat under semidry conditions and also in polluted environment faced regularly by them, which are otherwise totally uninhabitable to any typical freshwater teleosts. Furthermore, his group has recently demonstrated that the o-u cycle enzymes gets expressed at a very early stage of life cycle, which can also be induced under high external ammonia (Kharbuli et al., 2006)

Another unique observation made by Prof. Saha and his group, is the presence of the o-u cycle-related carbamyl phosphate synthetase I (CPS I) activity, which is normally present in higher vertebrates such as in mammals and amphibians, in addition to the presence of a typical fish type CPS III activity in two air-breathing teleosts (H. fossilis and C. batrachus) (Saha et al., 1997, 1999, 2007). This is again the first report of the presence of both types of o-u cycle-related CPSes (CPS I and III) in a single vertebrate species, which is otherwise normally not present together in a single vertebrate species. It was suggested that glutamine- and N-acetyl glutamate (NAG)-dependent CPS III, found in lower vertebrates, is the evolutionary precursor to ammonia- and NAG-dependent CPS I of ureotelic mammalian and amphibian species (Mommsen and Walsh, 1989, Science, 243: 72-75). Thus, the presence of both types of o-u cycle-related CPS activities in these air-breathing catfish has evolutionary significance with relation to the evolution of o-u cycle in vertebrates, in addition to their physiological significance.

Prof. Saha has also shown that although the air-breathing catfish (C. batrachus) possesses very efficient cell volume regulatory mechanisms liver, the hepatic cells remain partly swollen or shrunken states during hypo- and hypertonic exposures, respectively (Goswami and Saha, 2006) that can influence the carbohydrate metabolism and oxidative stress in C. batrachus; the hepatic cell swelling leads to stimulation of glycogenesis and hexose monophosphate pathway, inhibition of glycogenesis, gluconeogenesis and less oxidative stress, while the reverse is true during cell shrinkage (Goswami and Saha, 1998; Saha and Goswami, 2004; Goswami et al.,2004). All these observations indicate that this air-breathing catfish also possesses various physiological and biochemical adaptational strategies related to carbohydrate metabolism, thus enabling them to survive under osmotic, hypoxic and other environmentally-related stress problems, which they face in their natural habitat.

Furthermore, Prof. Saha has shown that the hypotonic cell swelling in C. batrachus liver causes stimulation of protein synthesis, inhibition of proteolysis and less production of nitric oxide through the inducible nitric oxide synthase; whereas the reverse is true during hypertonic cell shrinkage.

Prof. Saha, in his postdoctoral research work in Germany in collaboration with Prof. Häussinger, has shown definitely that the cell volume changes is the major determinant for the microtubule-dependent bile acid excretion by rat liver; cell swelling causes stimulation and cell shrinkage causes inhibition of bile acid excretion (Häussinger et al., 1992, 1993). Furthermore, he has also shown that the activation of Ca2+-dependent protein kinase C is the major factor of stimulating liver cholestasis, and finally liver serosis due to inhibition of canalicular transport of bile acids from liver (Kubitz et al., 2004). During liver cholestasis induced by the lipopolysaccharide, the multidrug resistance proteins the multidrug resistance protein (MRP) 3 and 5 get up-regulated as against the down-regulation of MRP2 in rat hepatocytes (Donner et al., 2004)

 

Number of M. Phil. /Ph. D. produced:

Ph. D. : 18

Name

Year

Title of Ph. D. Thesis

Dr. Jacqueline Dkhar

1995

Induction of urea cycle enzymes and characterization of arginase in a freshwater air-breathing teleosts, Heteropneustes fossilis Bloch.

Dr. Lipika Das

2001

Role of ureogenesis in a freshwater air-breathing catfish, Clarias batrachus under different environmental constraints

Dr. Supiya Dutta

2002

Amino acid metabolism in a freshwater air-breathing catfish Clarias batrachus under hyper-ammonia and osmotic stress.

Dr. Carina Goswami

2003

Mechanism of cell volume regulation and the effects of cell volume changes on glucose metabolism and oxidative stress in perfused liver of freshwater
air-breathing walking catfish, Clarias batrachus.

Dr. Bidyadhar Das

2004

Anthelmintic efficacy of Flemingia vestita: An in vitro study on carbohydrate metabolism in the cestode, Raillietina echinobothrida.

Dr. Zaiba Y. Kharbuli

2005

Purification and characterization of the urea cycle related carbamyl phosphate synthetase(s) and expression of urea cycle enzymes in a ureogenic air-breathing catfish, Clarias batrachus during early life stages.

Dr. Arundhati Bhattacharjee

2006

Studies on nitrogen metabolism in an air-breathing catfish, Clarias batrachus during osmotic stress.

Dr. Shritapa Datta

2006

Purification and characterization of glutamine synthetase and its regulation under various environmental stresses in an air-breathing catfish (Clarias batrachus).

Dr. Kuheli Biswas

2007

Biochemical characterization of nitric oxide synthases, nitric oxide production and protein turnover during cell volume changes in the hepatocytes of air-breathing catfish, Clarias batrachus.

Dr. Jamesteword L. Khongsngi

2010

Study of adaptive strategies against ammonia toxicity in the amphibious mud eel, Amphipnous cuchia.

Dr. Lucy M. Jyrwa

2011

Effect of osmotic, hyper-ammonia and desiccation stresses on gluconeogenesis in the air-breathing catfish, Clarias batrachus.

Dr. Mahua G. Choudhury

             

2012

Regulation and molecular characterization of different isoforms of nitric oxide production under environmental stress in the air-breathing catfish, Heteropneustes fossilis.

Dr. Gitalee Bhuyan

             

2013

Studies on tissue specific expression and induction of multiple glutamine synthetase genes under hyper-ammonia stress and ammonia-induced nitrotyrosynation of glutamine synthetase in catfish, Heteropneustes fossilis.

Dr. Manash Das

             

2014

Effect of osmotic stress on gluconeogenesis and mitogen activated protein kinases in the air-breathing catfish (Heteropneustes fossilis).

Dr. Hnunlalliani

2017

Influence of hyper-ammonia and dehydration stresses on the expression of multiple glutamine synthetase genes, heat shock protein 70 and mitogen-activated protein kinases in the mud eel, Monopterus cuchia.

Dr. Bodhisattwa Banerjee

2017

Molecular characterization of the expression of genes of glutamine synthetases and ornithine-urea cycle enzymes and the involvement of mitogen activated protein kinases under hyper-ammonia stress in the air-breathing catfish, Clarias batrachus (Bloch).

Dr. Priyanka Lal

2018

Studies on the influence of hyper-ammonia and desiccation stresses on the expression of mRNAs for ornithine-urea cycle enzymes, enzyme proteins and mitogen-activated protein kinases in the air-breathing catfish, Heteropneustes fossilis (Bloch).

Dr. Suman Kumari

2019

Effects of hyper-osmotic and hyper-ammonia stress on induction of genes for ornithine-urea cycle, amino acid metabolism-related enzymes and nitric oxide synthase in the air-breathing catfish Clarias magur (Hamilton).

M. Phil.: 1

Name

Year

Title of Thesis

Ms. Carina Goswami

1997

Glucose efflux and the rate of gluconeogenesis in perfused liver of a freshwater air-breathing teleosts, Clarias batrachus during cell volume changes.

 

Number of Ph. D. students working for the degree: 6

Name

Title of Ph. D. Dissertation

Mr. Debaprasad Koner 

Effects of titanium dioxide and zinc oxide nanoparticles and their bulk counterparts on oxidative stress in the air-breathing catfish Clarias batrachus (Bloch)

Ms. Rubaiya Hasan 

Environmentally-induced oxidative insults and antioxidant properties in air-breathing catfish, Clarias batrachus (Bloch)

Mrs. Annu Kumari 

Molecular characterization and expression of different osmosensitive transporter genes under osmotic stress in air-breathing catfish, Clarias magur (Hamilton)

Mr. Elvis Khongmawloh

Studies on molecular adaptations against the titanium dioxide nanoparticle-induced oxidative stress in primary hepatocytes of air-breathing catfish, Clarias magur (Hamilton).

Ms. Aquisha S. Lanong

Influence of lead nanoparticles on the expression of oxidative stress-related, inflammatory and heat shock protein genes in air-breathing catfish, Clarias magur (Hamilton).

Mr. Revelbornstar Snaitang

Effect of hyper-ammonia stress on amino acid metabolism-related and Hsp genes with the possible incorporation of ammonia to body protein in air-breathing stinging catfish, Heteropneustes fossilis.

 

Major Research Projects completed/in progress:

  1. Role of amino acid metabolism in Indian air-breathing teleosts to survive under hyper-ammonia stress. GTZ, Germany (1996-2000).

  2. Purification and characterization of carbamyl phosphate synthetase(s), and expression of urea cycle enzymes during early developmental stages in an amphibious potential ureogenic teleost, Clarias batrachus. UGC, New Delhi (2001-2004)

  3. Culture of carps and air-breathing fishes in hilly region and   transfer of technology to rural population of Meghalaya. DBT, New Delhi (2002-2005)

  4. Physiological significance of occurrence/expression and tissue distribution of nitric oxide synthases, production of nitric oxide under environmental constraints and pathological conditions in the air-breathing catfish, Heteropneustes fossilis. DST, New Delhi (2006-2009)

  5. Molecular and functional characterization of nitric oxide synthases and production of nitric oxide under environmental constraints and pathological conditions in the air-breathing catfish, Clarias batrachus. UGC, New Delhi (2007-2010)

  6. Influence of hyper-ammonia stress on the expression of multiple glutamine synthetase genes, mRNAs for ornithine urea cycle enzymes and mitogen activated protein kinases in air-breathing catfish, Heteropneustes fossilis. DST, New Delhi (2010-2013)

  7. Molecular characterization in the expression of mRNAs for ornithine-urea cycle enzymes and enzyme proteins, multiple glutamine synthetase genes and signaling cascades under hyper-ammonia stress in the air-breathing walking catfish, Clarias batrachus. DBT Twining, New Delhi (2011-2015).

  8. Effects of high environmental ammonia on the expression of multiple glutamine synthetase genes, mitogen-activated protein kinases and Hsp70 in the air-breathing mud eel, Monopterus cuchia. UGC, New Delhi

  9. Possible upregulation of ornithine-urea cycle genes and involvement of MAPKs to adapt under hyper-ammonia stress in air-breathing catfish, Clarias batrachus. DST-SERB, New Delhi (2014-2017)

  10. Molecular adaptation during exposure to zinc oxide and titanium dioxide nanoparticles with special reference to oxidative stress, nitric oxide production, expression of heat shock proteins in air-breathing catfish, Clarias batrachus. DST-SERB, New Delhi (2018-2021)

  11. To elucidate the unique biochemical adaptational strategies that allow two air-breathing catfishes (Clarias batrachus and Heteropneustes fossilis) to survive in ammonia enriched toxic waste. NASF-ICAR (2018-2021)

 

Major findings in research

       Prof. Saha has shown for the first time the unique presence of a functional ornithine-urea cycle (OUC) in two freshwater air-breathing catfish that are predominantly available in Indian subcontinent, such as Heteropneustes fossilis, Clarias batrachus (Saha and Ratha, 1987,1989; Saha et al., 1999), which otherwise is known to be non-functional or absent in typical fresh water teleosts. This unique finding by Prof. Saha has contradicted the earlier “gene deletion” hypothesis proposed by Brown and Cohen (1960) based on their findings of non-occurrence of functional OUC in fresh water teleosts, may be because of deletion of some genes required for OUC during their adaptive evolution in fresh water. In contrast, Prof. Saha and his group showed the existence of a functional OUC in air-breathing catfish, regulation of which depends on variable environmental constraints that they face regularly in natural habitats. For example, while living inside the mud-peat for months during the drought season under water restricted condition (Ratha et al. 1995; Saha et al., 2001), high concentration of ambient ammonia in stagnant water bodies due to evaporative water loss in summer (Saha and Ratha, 1990,1994; Saha and Das, 1999; Saha et al., 1995, 2003, 2007), and in alkaline condition (Saha et al., 2002), which compel them to switch over from ammoniotelic to ureotelic mode of nitrogen excretion by inducing the OUC enzyme activities. Although such unique adaptation was witnessed in amphibians, but not reported in any teleost species. In addition to this, Prof. Saha revealed existence of a functional OUC in non-hepatic tissues other than its usual presence in hepatic tissues, such as in kidney and muscle of these catfish as a special adaptation (Saha and Ratha, 1987, 1989; Saha et al., 1999), which is not found in higher vertebrates. Prof. Saha has also shown that these catfish have the capacity to accumulate very high concentration of ammonia while this is not so in mammals, where excess level of plasma ammonia may lead to coma and death.  Further, these catfish have the ability to convert the accumulated ammonia to glutamine and various non-essential amino acids very efficiently (Saha et al., 2000, 2002, 2007), as another unique adaptational strategy existing in these catfish. Another recent important contribution by Prof. Saha and his group is in relation to the occurrence of three glutamine synthetase (GS) genes expressed differentially in different tissues in catfish in contrast mammalian system, where the GS enzyme is encoded by only one gene, and all the three GS genes get induced specifically in different tissues under ammonia stress in high ambient ammonia (Banerjee et al. 2018).  His group has reported mitochondrial localization of both the isoforms of arginase (ARG 1 and 2), the last enzyme of the OUC, in C. batrachus liver, thereby suggesting that urea is exclusively synthetized inside the mitochondria of hepatic cells of catfish (Banerjee et al., 2017). This is again a unique observation in contrast to mammals, where urea is synthesised primarily in the cytosol of hepatic cells due to cytosolic localization of ARG, suggesting a regulatory role of mitochondrial urea synthesis in catfish.

       Prof. Saha made a significant revelation regarding the presence of two types of carbamyol phosphate synthetase (CPS), the CPS I (ammonia- and N-acetyl-L-glutamate-dependent), which is normally present in higher vertebrates such as in mammals and amphibians, in addition to the presence of a typical fish-type CPS III (glutamine- and N-acetyl-L-glutamate dependent) activity in air-breathing catfish (Saha et al., 1997, 1999, 2007). This is again another novel contribution of showing the presence of both the OUC-related CPSes (CPS I and III) in a single vertebrate species, which was not observed together in any other vertebrate. It was suggested that glutamine- and N-acetyl glutamate-dependent CPS III, found in lower vertebrates, is the evolutionary precursor to ammonia- and N-acetyl-L glutamate-dependent CPS I of ureotelic mammalian and amphibian species (Mommsen and Walsh, 1989). Thus, the presence of both types of OUC-related CPS activities in these two catfish probably has evolutionary significance with relation to the evolution of OUC in vertebrates, in addition to their physiological significance of efficient conversion of toxic ammonia to urea via the OUC by involving both the isoforms of CPS under ammonia stress.

     Prof. N. Saha and his group have also demonstrated the induction of nitric oxide (NO) synthesis by inducing the inducible nitric oxide synthase (NOS) gene under ammonia stress during exposure to high ambient ammonia and during mud-dwelling in air-breathing catfish (H. fossilis and C. batrachus) (Choudhury and Saha, 2012a,b; Kumati et al. 2018). He further suggested that the enhanced production of NO under ammonia stress, which is known to play diverse physiological functions in mammals under environmental stresses, is also playing a significant role in catfish in defending against the various ammonia-induced stressors as another adaptational strategy. His group has also recently demonstrated that enhanced production of endogenous NO can have antioxidant activity against the nanoparticle-induced oxidative stress in hepatocytes of air-breathing catfish (Koner et al. 2019).

 

Awards Received by Research Students:

Dr. Shritapa Datta:

  • Young Scientist Award by the Indian Science Congress Association, Kolkata (2004)
  • Swarna Jayanti Puroskar by the National Academy of Sciences, Allahabad (2007)

Dr. Kuheli Biswas:

  • Young Scientist Award by the Indian Science Congress Association, Kolkata (2007)

Dr. Mahua G. Choudhury:

  • President Dr. Shanakar Dayal Sharama Gold medal by the NEHU (2005)
  • Young Scientist Award by the Indian Science Congress Association, Kolkata (2010)
  • Swarna Jayanti Puroskar by the National Academy of Sciences, Allahabad (2012)
  • Dr. (Mrs.) Gouri Ganguly Memorial Award by the Indian Science Congress Association, Kolkata (2014)

Dr. Bodhisattwa Banerjee:

  • Young Scientist Award by the Indian Science Congress Association, Kolkata (2015)
  • NPDF by the SERB-DST for two years (2017-18)
  • Post-doctoral Fellowship to Israel for two years.

Publications:

National: 12
International: 46 

 

 

 

Updated by lakmen_zoology on Jun 26, 2019 11:40:17