Mechanisms of desiccation tolerance

The National Institute of General Medical Sciences awarded Southern Methodist University $399,927 on August 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to investigate the molecular mechanisms of desiccation tolerance in anhydrobiotic organisms.

The research deciphers how certain animals survive near-complete absence of water by identifying and characterizing protective molecules—specifically late embryogenesis abundant (LEA) proteins and small heat shock proteins (sHSPs)—that stabilize cellular structures during extreme dehydration. The investigator has previously isolated potent desiccation-protective 11-mer motifs from LEA proteins and demonstrated that sHSPs limit protein aggregation during water loss. Current work focuses on revealing the molecular mechanisms underlying these protective functions, contextualizing them across different cellular components and tissue types in living organisms, and employing functional screening methods to expand the repertoire of known protectants. The research carries potential applications to pharmaceutical storage and distribution, enabling room-temperature stabilization of vaccines, peptides, cells, and other biomedically relevant materials without dependence on cold-chain infrastructure.

The award supports work performed at Southern Methodist University's Dallas, Texas campus. The period of performance runs from August 1, 2026, through June 30, 2031. The assistance type is a Project Grant.

Abstract

Water is essential for life. IT provides stability for the macromolecular constituents of cells and is the solvent for the metabolism that powers life. Yet, some animals defy this logic and can survive in the near-complete absence of water. These desiccation-tolerant organisms are called anhydrobiotes. Although they were first identified in the early 1700S, we still have a very limited knowledge of how such organisms can withstand the extreme stress of desiccation. Defining the mechanisms that promote desiccation tolerance will reveal fundamental biochemical properties underlying cellular stability and stress tolerance. Defining protective mechanisms of dried cells is also likely to have far-reaching effects beyond the basic biology of anhydrobiotes. For example, many medicines rely on the cold chain for storage and distribution. The identification and development of new protectants may prove useful for stabilizing biomedically relevant materials such as cells, vaccines, peptides, or other medicines in a dried state at room temperature - reducing the need for a costly and wasteful cold chain for distribution. The broad goals of my research program are to decipher the molecular mechanisms by which some classes of protectants function and to expand the repertoire of known protectants. In the coming years, my lab will focus on two key classes of protectants: late embryogenesis abundant (LEA) proteins and small heat shock proteins (shsps). I previously identified 11-MER motifs from a LEA protein that are potent desicco-protectants and demonstrated that shsps can limit desiccation-induced protein aggregation. We now seek to reveal the molecular underpinnings of the protective capacity of these proteins. We also aim to contextualize these functions in vivo to decipher how different cellular components and tissue types can be protected. Additionally, we will employ innovative functional screening methods to discover new types of protectants that are individually sufficient for promoting desiccation survival. Collectively, this work is building towards a deeper understanding of how biological materials can be protected in a dried state. Ultimately, we seek to deduce principles for optimizing protectants that can be deployed to stabilize materials of biomedical relevance, contributing to the NIH mission to foster fundamental discoveries that will improve human health.