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=== Possible approaches === In their [[Web conferencing|Webinar]], [[DARPA]] outlined a number of possible research approaches for the Biostasis project. These approaches are based on research into [[diapause]] in [[tardigrade]]s and [[wood frog]]s which suggests that selective stabilization of intracellular machinery occurs at the [[protein]] level.<ref name=":1" /> ==== Protein chaperoning ==== In molecular biology, [[Chaperone (protein)|molecular chaperones]] are proteins that assist in the folding, unfolding, assembly, or disassembly of other [[Macromolecule|macromolecular]] structures. Under typical conditions, [[Chaperone (protein)|molecular chaperones]] facilitate changes in shape ([[conformational change]]) of [[macromolecule]]s in response to changes in environmental factors like [[temperature]], [[pH]], and [[voltage]]. By reducing conformational flexibility, scientists can constrain the function of certain proteins.<ref name=":2" /> Recent research has shown that proteins are promiscuous, or able to do jobs in addition to the ones they evolved to carry out.<ref name=":3">{{Cite news|url=https://www.sciencealert.com/the-apromiscuousa-protein|title=The 'Promiscuous' Protein|last=University|first=Massey|work=ScienceAlert|access-date=2018-05-26|language=en-gb}}</ref> Additionally, protein promiscuity plays a key role in the adaptation of species to new environments.<ref name=":3" /> It is possible that finding a way to control [[conformational change]] in promiscuous proteins could allow scientists to induce biostasis in living organisms.<ref name=":2" /> ==== Intracellular crowding ==== The crowdedness of cells is a critical aspect of biological systems.<ref>{{Cite magazine|url=https://www.wired.com/2012/10/how-intracellular-crowding-changes-everything/|title=How Intracellular Crowding Changes Everything|magazine=WIRED|access-date=2018-05-26|language=en-US}}</ref> Intracellular crowding refers to the fact that protein function and interaction with water is constrained when the interior of the cell is overcrowded.<ref name=":2" /> Intracellular [[organelle]]s are either membrane-bound vesicles or membrane-less compartments that compartmentalize the cell and enable [[Spatiotemporal pattern|spatiotemporal]] control of biological reactions.<ref>{{Cite journal|last1=Brangwynne|first1=Clifford P.|last2=Tompa|first2=Peter|last3=Pappu|first3=Rohit V.|date=2015-11-03|title=Polymer physics of intracellular phase transitions|journal=Nature Physics|language=En|volume=11|issue=11|pages=899β904|doi=10.1038/nphys3532|issn=1745-2473|bibcode=2015NatPh..11..899B}}</ref> By introducing these intracellular [[polymer]]s 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 ==== [[Tardigrade]]s are [[Micro-animal|microscopic animals]] that are able to enter a state of [[diapause]] and survive a remarkable array of environmental stressors, including [[freezing]] and [[desiccation]].<ref name=":0" /> Research has shown that [[intrinsically disordered proteins]] in these organisms may work to stabilize cell function and protect against these extreme environmental stressors.<ref>{{Cite journal|last1=Boothby|first1=Thomas C.|last2=Tapia|first2=Hugo|last3=Brozena|first3=Alexandra H.|last4=Piszkiewicz|first4=Samantha|last5=Smith|first5=Austin E.|last6=Giovannini|first6=Ilaria|last7=Rebecchi|first7=Lorena|last8=Pielak|first8=Gary J.|author-link8=Gary J. Pielak|last9=Koshland|first9=Doug|author-link9=Douglas Koshland|date=2017|title=Tardigrades Use Intrinsically Disordered Proteins to Survive Desiccation|url= |journal=Molecular Cell|language=en|volume=65|issue=6|pages=975β984.e5|doi=10.1016/j.molcel.2017.02.018|pmid=28306513|pmc=5987194|issn=1097-2765}}</ref> 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.<ref name=":2" /> This could allow larger animals to enter a state of biostasis similar to that of [[tardigrade]]s under extreme biological stress.
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