Research
My lab is interested in studying protein structure, function and its relation to human diseases. For some time DNA → RNA → Proteins appeared to be the central dogma of life but due to Nobel prize wining work of Christian Anfinsen (1972) and theoreticians like Cyrus Levinthal (Levinthal’s paradox 1969) the importance of protein folding code came to light and central dogma thus extended to DNA → RNA → Polypeptides → Functional Proteins. In other words, the forces or code responsible for maintaining protein in its proper 3D-structure and thus efficient function gained impetus in the last part of 20th century. The profound influence of this concept would soon be evident as mis-folded proteins (or toxic-folded) were found responsible for inclusion body problems in biotechnology projects and mis-fold triggered ordered protein aggregates “amyloid” were implicated in Prion, Alzheimer's and Parkinson's diseases. The amyloid has since been found involved in more than 50 human diseases. In addition, protein folding studies resulted in the discovery of a group of enzymes and proteins called “chaperones” that are responsible for helping maintain protein structure and function. We focus specifically on following areas:
1) Protein structure and function: We have been investigating the folding landscape of various proteins using chemical and thermal agents. In the process we have identified new folding intermediates of proteins and have contributed to the concept of mis-folding leading to amyloid formation especially using insulin as a model protein. Our articles published in this area have been cited more than 700 times.
Atta Ahmad (PhD)
N401 Howell Science Complex,
Department of Biology, Mail Stop 551
East Carolina University,
Greenville, NC, 27858
Ph: 252-737-4777
Email: ahmada@ecu.edu
2) Metal toxicity: We have shown calcium induces amyloid type aggregation of peptides Aβ40, Aβ42. Our studies further support the known implication of calcium in Alzheimer's diseases through Aβ40 and Aβ42. Further, we have shown copper induces structural modifications in protein α-synuclein (implicated in Parkinson’s) again leading to its amyloid type aggregation. Both metal ions exhibit this property at their physiological concentration and therefore, these studies have immediate application in understanding the important aspects that could further aid in the chelation therapy proposed for Alzheimer’s and Parkinson's.
3) Hsp70 family Chaperone: Chaperones are groups of enzymes and proteins that help other proteins attain structure essential for their function of which Hsp70 is an important family. If a protein fails to fold Hsp70 tags it for degradation (CHIP/ubiquitin pathway) and thus control the rate of ‘under-regulation/over-regulation’ of proteins or “proteostasis.” It is not known how chaperones are hijacked into uncontrolled over production of protein in the case of cancer or are not invoked during the mis-folded accumulation of proteins inside the cells. Since these proteins have not been investigated in detail the interactions between themselves and with substrate proteins is also not well characterized. Our efforts, in addition to addressing to each of these, also extends to screening chemical libraries to discover efficient modulators of chaperone systems for their immediate application to human disease systems mentioned above.
