U.S. Department of Health and Human Services
Rodolfo Ghirlando
 

 Contact Info

 
Tel: 301-451-8158
Email: rodolfog@intra.niddk.nih.gov
 

 Select Experience

 
  • Poste Vert FellowINSERM (National Institute of Health and Medical Research)1997
  • Visiting FellowNIDDK, NIH1995
  • Ph.D.Weizmann Institute of Science1991
  • B.Sc.University of the Witwatersrand1984
  • B.Sc. (Hons)University of the Witwatersrand1985
 

 Related Links

 

Rodolfo Ghirlando, Ph.D.

Staff Scientist, Office of the Chief, Laboratory of Molecular Biology
Specialties
  • Biomedical Engineering/Biophysics/Physics
  • Molecular Biology/Biochemistry
Research Summary/In Plain Language

Research Summary

Research Goal

The purpose of our studies is to understand in vivo chromatin structure at the 30-nm fiber level and beyond and to extend current hydrodynamic methodology for the study of challenging biomacromolecular interactions.

Current Research

Genomic DNA within the cell nucleus is packaged, together with histones and other functional proteins, into chromatin.  We are interested in understanding its organization within chromatin, as well as the topological constraints imposed upon it within the higher-order arrangement imposed by nonhistone proteins, such as CTCF.  These studies are important as they will allow us to better understand the structure of both the ‘open’ and condensed chromatin fiber in vivo.  Furthermore, as chromatin plays an essential role in processes such as DNA transcription, replication, repair, and recombination, its organization is fundamental to understanding the finer details of these processes.

Macromolecular interactions define most biological processes.  We utilize thermodynamic and hydrodynamic methods to characterize biological assemblies in terms of their shape, stoichiometry, and affinity of interaction.  These studies complement current biochemical, structural, and physiological investigations within the National Institute of Diabetes and Digestive and Kidney Diseases.  They further provide a platform for the development and improvement of current biophysical and thermodynamic methodologies, particularly analytical ultracentrifugation.

Applying our Research

It is now clear that the higher-order chromatin structure is intimately involved with nuclear processes such as DNA translation, replication, repair, and recombination. Recent studies have demonstrated that a number of human diseases are associated with abnormalities in these processes at the chromatin level.

Furthermore, the higher-order chromatin structure is maintained and regulated by a plethora of remodeling and modifying protein complexes. Mutations in some of these proteins have been associated with cancer and developmental disorders, altogether highlighting the significance of chromatin structure in proper gene regulation and disease. It is anticipated that an improved understanding of chromatin structure and its relation to related nuclear processes at a molecular level will help further unravel its connection to related abnormalities.

Need for Further Study

Research is still needed to understand the chromatin compaction on the chromosome level and to improve methodologies for the study of multiprotein/nucleic acid assemblies.