Laboratorio: Biología y Fisiología Celular

Instituto/Facultad

IHEM - CONICET - Facultad de Ciencia Médicas - Universidad Nacional de Cuyo (National University of Cuyo, Medical School )

Research interest

In the laboratory of Cell Biology and Physiology three main areas of research are conducted: a) the intracellular transport of macromolecules and its regulation, b) the secretory activity of male reproductive organs (eg, epididymis) and c) the biology of trypanosomatids and mechanisms of action of natural compounds on these parasites. .
Intracellular transport of macromolecules
Clathrin coated vesicle (CCV)-mediated transport is important in the Central Nervous System as it could have implications in maintaining the integrity and neuronal plasticity. Several models of nervous disorders may help explain the involvement of CCVs on the functionality of neurons. We are studying the expression and localization of coat proteins in different experimental models associated with neuronal alterations. It is also our interest to study the selective transport of lysosomal proteins, which is mediated by mannose 6-phosphate receptors. In this regard, we studied the participation of the MPRS in lysosomal biogenesis, and the possible changes that occur in the ligand-receptor system according to the metabolic conditions of the cells.
The mechanisms of secretion in mammalian epididymis
The mammalian epididymis plays a role in sperm maturation, due to their intense secretory activity. Furthermore, this organ is sensitive to changes in the androgenic hormones. For years, we have been studying the possible mechanisms of transport and secretion in the mammalian epididymis, and their hormonal regulation. These studies are conducted in whole animals and in cultured epididymal epithelial cells from various mammalian speciesUnderstanding the molecular basis of this secretion could explain the origin of certain dysfunctions which implies the existence of infertile spermatozoa.
Action of natural compounds on trypanosomatids.
Trypanosomatids are intracellular parasites that cause many severe diseases to humans. Trypanosoma cruzi is the causative agent of Chagas disease that affects millions of people in Latin America. Although much is known about the life cycle of the parasite and mode of transmission, there is still no effective therapy against the chronic phase of Chagas disease. In our laboratory we studied the effects of natural compounds on T. cruzi epimastigotes grown in liquid media, and intracellular parasites grown in mammalian cells. These projects include the identification of molecular targets for these compounds.

Principal Investigator

Miguel A. Sosa Escudero
                                     
Contact information

Phone: 54-261-4494143, extension: 2677
Fax: 54-261-4494117
msosa@fcm.uncu.edu.ar

Members

Dr. Miguel A. Sosa Escudero (PhD, Dr. In Biochemistry, Investigator CONICET, Associate Professor, Cellular and Molecular Biology, FCM-UNCuyo, Argentina)
Lic. Lorena Flavia Carvelli  (Lic. Biología Molecular, Postdoctoral fellowship, CONICET, Teaching Assistant, ICB-UNCuyo).

Lic. Patricia Andrea Barrera (Lic. Biología Molecular, Postdoctoral fellowship, CONICET, Teaching Assistant, ICB-UNCuyo).
Lic. Janina E. Borgonovo  (Lic. Bioquímica, Doctoral fellowship, CONICET)
Lic. Esteban Sebastian Lozano  (Lic. Biología Molecular, Doctoral fellowship, CONICET).
Lic. Andrea Carolina Aguilera  (Lic. Biología Molecular, Doctoral fellowship, CONICET, Teaching Assistant, ICB-UNCuyo).
Lic. Ana María Ruiz (Lic. Biochemistry, Associate Professor,  Biochemistry, Odontology Faculty, UNCuyo).

Technicians
Tirso Sartor (Technician CONICET)             

Recent publications (last 5 years)

•  Jimenez-Ortiz V, Brengio SD, Giordano O, Tonn C., Sanchez M., and Sosa MA (2005) The in vitro trypanocidal effect of two sesquiterpene lactones: helenalin and mexicanin. J Parasitology. 9 (1):170-174.
- Alberdi A, Sartor T, Sosa MA (2005) Binding of AP-2 clathrin adaptor complex to brain membranes is regulated by phosphorylation of proteins. Biochem Biophys Res Commun., 330:695-700
- Romano P, Lopez C, Carvelli L, Jofre G, Sartor T, Sosa MA.(2005) Developmental differences between cation-independent and cation-dependent mannose-6-phosphate receptors in rat brain at perinatal stages”. Dev Brain Res. 158:23-30.
- Sanchez M, Jimenez-Ortiz V, Sartor T, Tonn C, García EE, Nieto M, Burgos MH, Sosa MA (2006). Icetexane diterpene obtained from Salvia gilliessi is active against Trypanosoma cruzi.  Acta Tropica.  98(2):118-124.
Romano P, Lopez C, Carvelli L, Jofré G, Sartor T and Sosa MA (2006) Changes in phosphomannosyl ligands correlate with cation-dependent mannose-6-phosphate receptor in rat liver during perinatal development.  Biochem. Biophys. Res. Commun.  344(2):605-611.
Baiardi G., Ruiz AM, Beling A, Landa  A,  Sosa MA, Gargiulo P (2007) Glutamatergic ionotropic blockade disrupts working memory and might alter the endocytic machinery in the rat accumbens and prefrontal cortex. J Neural Transm, 114:1519-1528..
Romano P, Sosa MA (2008) Posibles roles de los receptores a manosa-6-fosfato durante la organogénesis. Revista Médica Universitaria. UNCuyo. ISSN 1669- 8991
Barrera P, Jimenez-Ortiz V, Giordano O, Tonn C, Galanti N, and Sosa MA (2008) Natural sesquiterpene lactones are active against Leishmania mexicana possible by multiple effects. J Parasitol, 94(5):1143-9.
Jiménez-Ortiz V, Paredes R, Sosa MA, and Galanti N (2008) Natural occurrence of programmed cell death in T.cruzi epimastigotes maintained in axenic culture.  J Cell Biochem, 2008 Oct 15;105(3):688-98.
Jofré, G.F., Balmaceda, V., Sartor, T., Carvelli, L., Barrera, P., and Sosa, M.A (2008) Organ specific changes in the expression of cation-dependent and cation-independent mannose-6-phosphate receptors during perinatal development in rats. Cells Tissues and Organs. 2008 Sep 30. [Epub ahead of print]. (2009) Vol. 190, No. 1,  pp 27 – 33. Doi: 10.1159/000000000. 190:27-33.
Aguilera Merlo, C., Fogal T, Sartor T., Domínguez S, Sosa MA, Scardapane L, and Piezzi R (2009) Ultrastructural and biochemical changes in epididymal corpus and cauda of Vizcacha (Lagostomus maximus maximus). J Morphol, 270(7):805-814.
 Borgonovo J, Seltzer A, Sosa MA (2009) Acute  intrastriatal administration  of quinolinic acid alters expression and distribution of AP-2 adaptors. Possible implications in the endocytotic machinery. J Neural Transm,  116(10): 1201-1208.
Sülsen V, Barrera P, Muschietti L, Martino V,  Sosa MA  (2010) Antiproliferative effect and ultrastructural alterations induced by psilostachyin on trypanosoma cruzi. Molecules, 15:545-553.

Present support

Compuestos de origen natural con actividad sobre Trypanosoma cruzi y Leishmania sp. Estudio de su actividad in vitro, in vivo y de sus mecanismos de acciön. PIP 112-200801-01540. 2009-2011.
Molecular mechanisms of regulated exocytoses required in fertilization. MINCyT Agencia Nacional de Promoción Científica y Técnica. PICT2005-38364. 2007-2010.

Internal collaborations

Our laboratory works in close collaboration with groups in the IHEM leaded by
Alicia Seltzer
And from IMBECU leaded by
Pascual Gargiulo
Adriana Gonzalez

International collaborations

Dr. Norbel Galanti :  Instituto de Ciencias Biomédicas (ICBM)
Laboratorio de Biología Celular y Molecular
Universidad de Chile

Dr. Renato Mortara:  Departamento de Microbiologia, Imunologia e Parasitologia
UNIFESP - Escola Paulista de Medicina

Teaching activity
The members of the Laboratory are involved in the following courses
De las Moléculas a las Células (From Molecules to the Cell). For undergraduate students, Medical School .

Biochemistry. For undergraduate students, Instituto de Ciencias Básicas (Institute of Basic Science), UNCuyo.
Cell Biology. For undergraduate students, Instituto de Ciencias Básicas (Institute of Basic Science), UNCuyo.

Biología Celular y Molecular (Cell and Molecular Biology). Graduate student. Biology Doctoral Program (PROBIOL)

Thesis completed

1996-1999 Sivia Belmonte, Bioquímica (Universidad J A Maza). Doctorado Fac. de Farmacia y Bioquímica, Universidad Nacional de San Luis. Tema " Interacción de Proteínas epididimarias con espermatozoides de rata. Receptores de membrana que reconocen azúcares fosforilados ". Aprobada (sobresaliente).

1996-2001 Antonio Alberdi, Lic. en Genética de la Universidad Nacional de Misiones. Programa de Postgrado en Biología (PROBIOL) U.N. Cuyo. Tema La regulación de la formación de vesículas cubierta ". Aprobada (distinguido)

1998-2003 Patricia Romano, Bioquímico de la UJAM. Programa de Postgrado en Biología (PROBIOL) U.N. Cuyo. Tema: Estudio del rol de receptores a manosa-6-fosfato. Sobresaliente.

2001-2006 Verónica Jiménez Ortiz, Bioquímico de la UJAM  Programa de doctorado de la Universidad de Chile. Tema:  Muerte celular programada e identificación de canales iónicos en Tripanosoma cruzi Sobresaliente.

Actualizado Noviembre 2010