Director: Professor Yury O. Chernoff, School of Biology, Georgia Institute of Technology - (video )
Mission: to develop new technologies for detecting, monitoring and controlling self-assembled macromolecular complexes at various levels, including their pathogenic consequences, biological roles and evolutionary origins.
Accordingly, the Center will utilize the combined expertise of Georgia Tech and Emory University researchers who employ a variety of in vivo, in vitro and in silico approaches and represent different fields of study, including: genetics; molecular, cellular and structural biology; chemistry, biochemistry and synthetic biology; chemical, biomolecular and biomedical engineering; bioinformatics and computational biology.
• Neurological disorders such as Alzheimer, Parkinson, and Huntington diseases, caused by self-assembled protein nanostructures (amyloids and neural inclusions), represent a serious challenge to future health care. These diseases are usually fatal and age-dependent, and health care costs associated with them are tremendous. For example, Alzheimer disease affects 50% of people aged over 85. Therefore, impact of these diseases will only grow with the eradication of other diseases and an increase in human life span.
• Amyloid diseases and other macromolecular assembly disorders could be of both sporadic and genetic nature, and little is known about environmental or physiological conditions promoting them, making it difficult to develop the prevention and prophylactic procedures. Early diagnosis of amyloid diseases is also not available in most cases.
• Infectious amyloids (prions) cause transmissible encephalopathies such as “mad cow” disease, elk and deer chronic wasting diseases, or human Creutzfeldt-Jacob disease, and may spread via medical mistreatment, blood transfusions, or from domestic animals to humans consuming infected meat. Due to their long incubation periods, prion diseases are extremely difficult to monitor.
• Studies of prion proteins in lower eukaryotes such as yeast have demonstrated that amyloid and prion diseases originate from malfunctioning of evolutionarily conserved mechanisms governing the assembly of multi-molecular structures. Yeast and fungal prions behave as heritable elements transmitted via cytoplasm. In this way, information coded in the structure rather in the sequence could become heritable and reproducible in generations. Another example of structural templating is provided by inheritance of the surface structures in some protozoa. Appreciation of the role of structural inheritance in evolution is only beginning to unfold.
• Some amyloids and amyloid-like assemblies play biologically positive roles, for example by protecting cells against freezing and other stresses, scaffolding polymerization of covalent polymers such as melanin, storing peptide hormones, or controlling attachment of fungi and bacteria to their substrates. Self-assembled intracellular structures formed on the principles that are similar to amyloid formation are involved in protection against stresses, and storage or degradation of RNAs and components of the translational machinery. Many proteins can acquire amyloid form in certain conditions, suggesting that amyloid represents an ancient protein fold possibly involved in structure formation at early stages of biological and prebiotic evolution.
• Amyloid-like polymers such as silks have a long history of technological use. Amyloids were utilized for construction of self-assembled nanowires and could be applied to other technological purposes.