Structural and functional study of human hemoglobin variants

• Grant number: 15/13710-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2015
• End date: August 31, 2019
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Maria de Fatima Sonati
• Grantee: Susan Elisabeth Domingues Costa Jorge
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches, AP.TEM

Abstract

The sub-project "Structural and Functional Study of Human Hemoglobin Variants" (Principal Investigator: Maria Fatima Sonati) is part of the thematic project "Diseases of Red Blood Cells: Pathophysiology and New Therapeutic Approaches" (Coordinator: Fernando Ferreira Costa). Your goal is, through computational and experimental techniques, to study changes in the allosterism of the human hemoglobin that modify its functional properties as well as the protein stability, in structural variants associated with clinical and hematological important alterations. It is intended to obtain broaden and deepen structural and functional studies of abnormal human hemoglobins detected in our population, using techniques such as protein crystallization, SAXS (X-ray scattering at low angles), Raman spectroscopy, Circular Dichroism and eventually Electron Microscopy High Definition. From the computational point of view, more detailed techniques of molecular dynamics analysis must be applied. It is expected that, in addition to better characterize the structural variants being studied, such work enables better understanding of aspects of structural dynamics of native Hb through loss, substitution or insertion of residues that promote different biophysical responses.

Scientific publications

(5)

(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)

PEDROSO, GISELE A.; KIMURA, ELZA M.; SANTOS, MAGNUN N. N.; ALBUQUERQUE, DULCINEIA M.; MALIMPENSA, DANAE; JORGE, SUSAN E.; VERISSIMO, MONICA P. A.; COSTA, FERNANDO F.; SONATI, MARIA F.. Thalassemia major phenotype caused by HB Zurich-Albisrieden [alpha 2 59(E8) Gly > Arg (HBA2:C.178G > C)] in a Brazilian child. PEDIATRIC BLOOD & CANCER, v. 65, n. 12, DEC 2018. (14/00984-3, 15/13710-1)

JORGE, S. E.; BRINGAS, M.; PETRUK, A. A.; ARRAR, M.; MARTI, M. A.; SKAF, M. S.; COSTA, F. F.; CAPECE, L.; SONATI, M. F.; ESTRIN, D.. Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra. Archives of Biochemistry and Biophysics, v. 637, p. 73-78, JAN 1 2018. (14/00984-3, 15/13710-1)

PEDROSO, G. A.; FERNANDES, P.; JORGE, S. E. D. C.; NASCIMENTO, P. H.; LIMA, P. C.; GRIGOLETO, M. R. P.; ALBUQUERQUE, D. M.; SANTOS, M. N. N.; COSTA, F. F.; TORO, A. A. D. C.; et al. Hemoglobin Kirklareli [Alpha(2) 59(E7) His >>Leu; HBA2:c.176A > T] in a Brazilian child with severe dyspnea and low O-2 saturation. ANNALS OF HEMATOLOGY, v. 98, n. 12, p. 2853-2855, DEC 2019. (15/13710-1, 14/00984-3)

JORGE, S. E.; LANARO, C.; ALBUQUERQUE, D. M.; NASCIMENTO, P. H.; PEDROSO, G. A.; OLIVEIRA, S. C.; GRIGOLETO, M. R. P.; SANTOS, M. N. N.; COSTA, F. F.; SONATI, M. F.. Hb Fairfax [HBB:c.285_286insGAGCTGCACTGTGAC] in a Brazilian patient with severe hemolytic anemia-identification and functional study. ANNALS OF HEMATOLOGY, v. 98, n. 9, p. 2253-2255, SEP 2019. (15/13710-1, 14/00984-3)

PEDROSO, GISELE A.; KIMURA, ELZA M.; SANTOS, MAGNUN N. N.; ALBUQUERQUE, DULCINEIA M.; FERRUZZI, JUCILANE L. H.; JORGE, SUSAN E.; COSTA, FERNANDO F.; SAAD, SARA T. O.; SONATI, MARIA F.. Coinheritance of Hb Bristol-Alesha [beta 67(E11)Val -> Met; HBB: c.202G > A] and the alpha 212 Patchwork Allele in a Brazilian Child with Severe Congenital Hemolytic Anemia. HEMOGLOBIN, v. 41, n. 3, p. 203-208, 2017. (14/00984-3, 15/13710-1)