Biostasis

Biostasis is the ability of an organism to tolerate environmental changes without having to actively adapt to them. Biostasis is found in organisms that live in habitats that likely encounter unfavorable living conditions, such as drought, freezing temperatures, change in pH levels, pressure, or temperature. Insects undergo a type of dormancy to survive these conditions, called diapause. Diapause may be obligatory for these insects to survive. The insect may also be able to undergo change prior to the arrival of the initiating event.[1]

Biostasis is also used as a synonym for the terms cryostasis or cryonics. Cryonics is a medical procedure concept that is a well established trope in Science Fiction, that may at some point in the future become a possible option for individuals who are terminally ill. The patients would be frozen in what is known as cryonic suspension. The patients are frozen so that when technology advances both to enable them to be unfrozen and brought back to life but also for their illness to be treated, they can be re-animated and their disease can be cured or treated.[2]

Current Research

On March 1, 2018, the Defense Advanced Research Projects Agency (DARPA) announced their new Biostasis program under the direction of Dr. Tristan McClure-Begley. The aim of the Biostasis program is to develop new possibilities for extending the golden hour in patients who suffered a traumatic injury by slowing down the human body at the cellular level, addressing the need for additional time in continuously operating biological systems faced with catastrophic, life-threatening events. By leveraging molecular biology, the program aims to control the speed at which living systems operate and figure out a way to "slow life to save life."[3]

On March 20, 2018, the Biostasis team held a Webinar which, along with a Broad Agency Announcement (BAA), solicited five-year research proposals from outside organizations. The full proposals were due on May 22, 2018.[4]

Possible Approaches

In their Webinar, DARPA outlined a number of possible research approaches for the Biostasis project. These approaches are based on research into diapause in tardigrades and wood frogs which suggests that selective stabilization of intracellular machinery occurs at the protein level.[3]

Protein Chaperoning

In molecular biology, molecular chaperones are proteins that assist in the folding, unfolding, assembly, or disassembly of other macromolecular structures. Under typical conditions, molecular chaperones facilitate changes in shape (conformational change) of macromolecules in response to changes in environmental factors like temperature, pH, and voltage. By reducing conformational flexibility, scientists can constrain the function of certain proteins.[4] Recent research has shown that proteins are promiscuous, or able to do jobs in addition to the ones they evolved to carry out.[5] Additionally, protein promiscuity plays a key role in the adaptation of species to new environments.[5] It is possible that finding a way to control conformational change in promiscuous proteins could allow scientists to induce biostasis in living organisms.[4]

Intracellular Crowding

The crowdedness of cells is a critical aspect of biological systems.[6] Intracellular crowding refers to the fact that protein function and interaction with water is constrained when the interior of the cell is overcrowded.[4] Intracellular organelles are either membrane-bound vesicles or membrane-less compartments that compartmentalize the cell and enable spatiotemporal control of biological reactions.[7] By introducing these intracellular polymers to a biological system and manipulating the crowdedness of a cell, scientists may be able to slow down the rate of biological reactions in the system.

Tardigrade-disordered Proteins

Tardigrades are microscopic animals that are able to enter a state of diapause and survive a remarkable array of environmental stressors, including freezing and desiccation.[1] Research has shown that intrinsically disordered proteins in these organisms may work to stabilize cell function and protect against these extreme environmental stressors.[8] By using peptide engineering, it is possible that scientists may be able to introduce intrinsically disordered proteins to the biological systems of larger animal organisms.[4] This could allow larger animals to enter a state of biostasis similar to that of tardigrades under extreme biological stress.

References

  1. 1 2 Karen Lindahl and Susie Balser (2 October 1999). "Tardigrade Facts". Illinois Wesleyan University. Retrieved 14 September 2016.
  2. ↑ Merkle, R.C. (September 1992). "The technical feasibility of cryonics". Medical Hypotheses. 39: 6–16. doi:10.1016/0306-9877(92)90133-w.
  3. 1 2 "Slowing Biological Time to Extend the Golden Hour for Lifesaving Treatment". www.darpa.mil. Retrieved 2018-05-21.
  4. 1 2 3 4 5 "Rapid Threat Assessment (RTA)" (PDF). www.darpa.mil. Retrieved 2018-05-21.
  5. 1 2 University, Massey. "The 'Promiscuous' Protein". ScienceAlert. Retrieved 2018-05-26.
  6. ↑ "How Intracellular Crowding Changes Everything". WIRED. Retrieved 2018-05-26.
  7. ↑ Brangwynne, Clifford P.; Tompa, Peter; Pappu, Rohit V. (2015-11-03). "Polymer physics of intracellular phase transitions". Nature Physics. 11 (11): 899–904. doi:10.1038/nphys3532. ISSN 1745-2473.
  8. ↑ Boothby, Thomas C.; Tapia, Hugo; Brozena, Alexandra H.; Piszkiewicz, Samantha; Smith, Austin E.; Giovannini, Ilaria; Rebecchi, Lorena; Pielak, Gary J.; Koshland, Doug (2017). "Tardigrades Use Intrinsically Disordered Proteins to Survive Desiccation". Molecular Cell. 65 (6): 975–984.e5. doi:10.1016/j.molcel.2017.02.018. ISSN 1097-2765.

9. Oliver, James D. "The viable but nonculturable state in bacteria." The Journal of Microbiology 43.1 (2005): 93-100.

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