Characterization of the calcium release-activated (CRAC) channel in the human pathogen Schistosoma mansoni through the study of its components STIM and ORAI proteins

• Grant number: 16/12505-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 01, 2016
• End date: September 30, 2017
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Ana Paula Ulian de Araujo
• Grantee: Ana Eliza Zeraik
• Supervisor: Patrick Gerald Hogan
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Institution abroad: La Jolla Institute for Allergy and Immunology (LIAI), United States
• Associated to the scholarship: 13/20715-4 - Studies of the correlation between septin dynamics and Ca2+ homeostasis in muscular cells from Schistosoma mansoni, BP.PD

Abstract

The present research project aims to study the proteins that comprise the calcium release-activated (CRAC) channel (STIM and ORAI) from the important human pathogen Schistosoma mansoni to get insights into the gating mechanism of the parasite CRAC channel. The association of septins to this channel will also be investigated by the impairment of its dynamics (using FCF) and evaluation of the effect on reconstituted schistosome CRAC channel. The described activities will be performed by Ana Eliza Zeraik during her proposed one year long stay at La Jolla Institute for Allergy and Immunology, under the supervision of Prof. Patrick Hogan. Two different systems will be used in the study of S. mansoni CRAC channel: one expressing all components in mammalian cells and another by reconstituting in lipossomes a ORAI channel expressed in S. cerevisiae and use several cytoplasmic constructs of STIM, some of which that have already been produced by us in E. coli. This will allow to study in more detail the interaction of ORAI with STIM and its influence in calcium transport. Ca2+ is essential for diverse biological processes and is involved in a multitude of signaling processes. There is a significant divergence on the sequence of STIM and ORAI from S. mansoni when compared to the human orthologues, and many anti-parasitic agents alter parasite Ca2+ homeostasis, such as the main drug used against schistosomiasis, thus the characterization of this Ca2+ channel in schistosomes might reveal new potential targets against schistosomiasis. Due to the inherent difficulties in working with STIM and ORAI, the expertise of Prof. Hogan, and the infrastructure provided by the La Jolla Institute, are essential to the success of the project.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GUDLUR, APARNA; ZERAIK, ANA ELIZA; HIRVE, NUPURA; RAJANIKANTH, V.; BOBKOV, ANDREY A.; MA, GUOLIN; ZHENG, SISI; WANG, YOUJUN; ZHOU, YUBIN; KOMIVES, ELIZABETH A.; et al. Calcium sensing by the STIM1 ER-luminal domain. NATURE COMMUNICATIONS, v. 9, OCT 31 2018. (16/12505-8)

GUDLUR, APARNA; ZERAIK, ANA ELIZA; HIRVE, NUPURA; HOGAN, PATRICK G.. STIM calcium sensing and conformational change. JOURNAL OF PHYSIOLOGY-LONDON, v. 598, n. 9, SI, p. 1695-1705, MAY 2020. (16/12505-8)