RBernal-01
Cryo-EM Structural Investigation Chaperonin Mediated Protein Folding Intermediates
Dr. Ricardo Bernal
Health, human disease & diagnostics
Preferred major field of study or minimum required skills
Basic Chemistry and Biology knowledge is required and everything else can be learned on the job.
Scholarly significance/intellectual merit
The proteome is a vast collection of proteins each of which contribute to the maintenance of cellular homeostasis. Diverse environmental and physiological stressors can lead to various deleterious effects including structural damage of proteins. With so many threats overwhelming the integrity of the proteome it is imperative that the cell ensures a robust defense mechanism to keep its proteins structurally viable and functional. Cellular stressors such as heat shock can often result in partial protein misfolding that can then lead to various disorders including neurodegeneration. The integrity of protein structure and function is maintained by a class of proteins known as molecular chaperones. These molecular chaperones sustain protein homeostasis through assistance with protein folding or the stabilization of partially misfolded proteins. A subclass of molecular chaperones, known as heat shock proteins, can assist in the folding of nascent polypeptides or aid in the stabilization and the refolding of non-native proteins. They are also involved in other pathways such as degradation of irreversibly damaged proteins and unfolding of other proteins for translocation across a membrane. In summary, these chaperonins are absolutely required for life and the development of diseases.
Research question(s)
The main objective is to purify and carry out biological activity assays on our molecular chaperones using various denatured substrates and to determine the strength of those interactions so we can begin to understand their effect on the human diseases they are causing.
Methods/techniques/instruments to be learned/utilized
Protein expression, protein chromatography, dynamic light scattering, Spectrophotometry for biological activity assays, surface plasmon resonance, perhaps even structure determination using cryo-EM.