INTERPLAY OF BIOLOGICAL AND PHYSICAL PROCESSES IN OTOCONIAL MORPHOGENESIS

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Otoconia are biomineral particles of microscopic size essential for perception of gravity and maintenance of balance. Millions of older Americans are affected in their mobility, quality of life, and health by a progressive demineralization of otoconia. Currently no effective means to prevent or counteract this process are available. In other systems, such as bone and teeth, initiative research has yielded spectacular results in prevention, alleviation and repair of mineral deficiencies. In the past few years numerous biomolecules involved in the morphogenesis of otoconia have been identified. Our objective is to elucidate the biochemical and biophysical properties of selected otoconial matrix proteins underlying interaction with the mineral phase in the control of nucleation and direct crystal growth. Biophysical characterization relies on two complementary techniques, solution state determination by means of traditional biophysical techniques as well as the recently developed High Resolution Mass Spectrometric techniques. A different approach assesses the influence of these matrix proteins upon calcite crystal growth in vitro, evaluated by SEM and Raman Spectrometry. Availability of sufficient quantities of matrix proteins is an essential prerequisite for these studies to be achieved by recombinant techniques by means of mammalian expression systems. Reliance upon recombinant protein production is the fundamental innovation of this approach, which liberates otoconial research from the constraints of microscopic size and difficult accessibility. This effectively places otoconial research on equal footing with much larger and readily accessible mineralized structures. It is hoped that the assembled interdisciplinary team will serve as nucleus for the development of a dedicated otoconial research program. Ultimately our findings should have impact on the quality of life of the aged, as well as patients specifically afflicted with otoconial dysfunctions, such as benign positional paroxysmal vertigo (BPPV). Otoliths and otoconia (from Latin 'stones' and 'sand', respectively) play an essential role in the maintenance of balance. In the normal aging process and in numerous diseases otoconia gradually degenerate, eventually resulting in loss of balance, falls and bone fracture. Falls are the leading cause of accidental death in the elderly population. We intend to study the formation, maintenance and vulnerability of otoconia using a combination of biochemical and biophysical approaches. Information gained should ultimately provide means to slow down the deleterious effects of aging on otoconia, in a manner similar to our ability to prevent and/or ameliorate dental caries or osteoporosis.