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Seetharaman Parashuraman

Research Focus : Organization and function of the mammalian secretory pathway

Organization, spatial and temporal, is a fundamental feature of life. The form and function of an organism is determined by the organization of its molecular constituents. The last decade had exploded with "omics" technologies that have given us the parts list of many organisms including our own. The next challenge is in elucidating the organizing principles that dictate the interactions between these constituents leading to the emergence of life as we see it.
We use the secretory pathway of the eukaryotic cell as a model system to understand these principles. The eukaryotic cell consists of intracellular membrane-bound compartments of which the secretory pathway forms a major part. Nearly 1000 proteins are localized to it and about one-third of the proteins encoded by our genome depend on it for their biosynthesis and proper localization. Apart from the proteins, the secretory pathway also contributes to the biosynthesis of most of the lipids present in eukaryotic cell and polysaccharides (like scales in the case of algae).

To get a systems perspective of the secretory pathway we pursue answers to these following questions:
1) How do the constituents of the pathway interact to promote the specific morphological and functional features to the secretory pathway?
2) What are the contributions of the pathway to the cellular physiology ?
3)How are the secretory pathway functions regulated ? 
4) What are the physiological and evolutionary significance of such an organization? 

We study the mammalian Golgi apparatus to answer these questions and we do so by actively following these research directions:

1) Understanding the functional organization of the Golgi: The Golgi apparatus is a dynamically stable compartment with well-differentiated molecular and/or structural zones. We would like to understand how this organization contributes to the transport and processing (glycosylation) functions of the organelle. To this end, we are building a molecular map of the Golgi apparatus and are interrogating the contribution of the specific spatio-temporal molecular organization to the functioning of the organelle. (For more information contact: , Marinella Pirozzi)

2) Regulation of the secretory pathway: Here we focus on the regulation of the initial stages of the secretory pathway viz. the protein biosynthesis, folding and degradation in the Endoplasmic reticulum. Using the disease model of Cystic Fibrosis, we had recently found a set of regulatory pathways that regulate the ER associated degradation of proteins. We further exploring to understand how these pathways act and if they can be of therapeutic utility. (For more information contact: , Seetharaman Parashuraman)

3) Functional interaction of Secretory pathway with other modules of the cell: The secretory pathway does not function in isolation and is integrated with other cellular functions (modules) of the cell. We are exploring and defining such relationships, using transcriptomics, in order to create an integrated functional map of the cell (from the perspective of the secretory pathway). (For more information contact: )

Curriculum

  • Ph.D., in life sciences from National Institute of Immunology (Jawaharlal Nehru University), New Delhi, India.
  • Post-doctoral fellow: Mario Negrisud Institute, S.Maria Imbaro, Italy (2005-2009)
  • Post-doctoral fellow: Telethon Institute of Genetics and Medicine, Naples, Italy (2009-2012).
  • Researcher: Institute of Protein Biochemistry, National Research Council, Naples, Italy (2012-2014)
  • Head, Microscopy facility, Institute of Protein Biochemistry, National Research Council, Naples, Italy (2014 - ) 
  • Senior Researcher, Institute of Protein Biochemistry, National Research Council, Naples, Italy (2014 - )

 

PUBLICATIONS:

1. Rizzo R, Parashuraman S, Luini A. Correlative video-light-electron microscopy: development, impact and perspectives. Histochem Cell Biol. 2014 Aug;142(2):133-8. 

2. Beznoussenko GV*, Parashuraman S*, Rizzo R, Polishchuk R, Martella O, DiGiandomenico D, Fusella A, Spaar A, Sallese M, Capestrano MG, Pavelka M, Vos MR, Rikers YG, Helms V, Mironov AA, Luini A. Transport of soluble proteins through the Golgi occurs by diffusion via continuities across cisternae. Elife. 2014 May 27:e02009. 

3. Rizzo R *, Parashuraman S*, Puri C, Lucocq J, Luini A. The dynamics of engineered resident proteins in the mammalian Golgi complex relies on cisternal maturation. J. Cell. Biol. Jun 24;201(7):1027-36.. 

4. Madan R, Rastogi R, Parashuraman S, Mukhopadhyay A. Salmonella acquires lysosome-associated membrane protein 1 (LAMP1) on phagosomes from Golgi via SipC protein-mediated recruitment of host Syntaxin6. J. Biol. Chem. 2012. 287(8): 5574-87. 

5. Parashuraman S *, Madan R *, Mukhopadhyay A. NSF independent fusion of Salmonella-containing late phagosomes with early endosomes. FEBS Lett. 2010. 584(6): 1251-6. 

6. Parashuraman S, Mukhopadhyay A. Assay and functional properties of SopE in the recruitment of Rab5 on Salmonella-containing phagosomes. Methods Enzymol. 2005. 403: 295-309. 

7. Mukherjee K, Parashuraman S, Krishnamurthy G, Majumdar J, Yadav A, Kumar R, Basu SK, Mukhopadhyay A. Diverting intracellular trafficking of Salmonella to the lysosome through activation of the late endocytic Rab7 by intracellular delivery of muramyl dipeptide. J. Cell Sci. 2002. 115(Pt 18): 3693-701. 

8. Mukherjee K, Parashuraman S, Raje M, Mukhopadhyay A. SopE acts as an Rab5-specific nucleotide exchange factor and recruits non-prenylated Rab5 on Salmonella containing phagosomes to promote fusion with early endosomes. J Biol. Chem. 2001. 276(26): 23607-15. 

* - denotes equal contribution

Group

Group leader
Seetharaman Parashuraman

Researcher
Marinella Pirozzi :

Graduate student
Prathyush Roy : Sonali Chavan :