Biostasis or

Cryptobiosis Cryptobiosis or anabiosis is a metabolic state of life entered by an organism in response to adverse environmental conditions such as desiccation, freezing, and oxygen deficiency. In the cryptobiotic state, all measurable metabolic processes stop ...

is the ability of an

organism In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and ...

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 In animal dormancy, diapause is the delay in development in response to regular and recurring periods of adverse environmental conditions.Tauber, M.J., Tauber, C.A., Masaki, S. (1986) ''Seasonal Adaptations of Insects''. Oxford University Press It ...

. 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.

Microorganisms

Biostasis in this context is also synonymous for viable but nonculturable state. In the past when

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

were no longer growing on culture media it was assumed that they were dead. Now we can understand that there are many instances where bacteria cells may go into biostasis or suspended animation, fail to grow on media, and on resuscitation are again culturable. VBNC state differs from 'starvation survival state' (where a cell just reduces

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

significantly). Bacteria cells may enter the VBNC state as a result of some outside stressor such as "starvation, incubation outside the temperature range of growth, elevated osmotic concentrations (seawater), oxygen concentrations, or exposure to white light". Any of these instances could very easily mean death for the bacteria if it was not able to enter this state of dormancy. It has also been observed that in may instances where it was thought that bacteria had been destroyed (

pasteurization Pasteurization or pasteurisation is a process of food preservation in which packaged and non-packaged foods (such as milk and fruit juices) are treated with mild heat, usually to less than , to eliminate pathogens and extend shelf life. The ...

of milk) and later caused spoilage or harmful effects to consumers because the bacteria had entered the VBNC state. Effects on cells entering the VBNC state include "dwarfing, changes in metabolic activity, reduced nutrient transport, respiration rates and macromolecular synthesis". Yet

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

continues, and shock proteins are made. Most importantly has been observed that ATP levels and generation remain high, completely contrary to dying cells which show rapid decreases in generation and retention. Changes to the cell walls of bacteria in the VBNC state have also been observed. In

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

a large amount of cross-linking was observed in the peptidoglycan. The autolytic capability was also observed to be much higher in VBNC cells than those who were in the growth state. It is far easier to induce bacteria to the VBNC state and once bacteria cells have entered the VBNC state it is very hard to return them to a culturable state. "They examined nonculturability and resuscitation in

Legionella pneumophila ''Legionella pneumophila'' is a thin, aerobic, pleomorphic, flagellated, non-spore-forming, Gram-negative bacterium of the genus ''Legionella''. ''L. pneumophila'' is the primary human pathogenic bacterium in this group and is the causative age ...

and while entry into this state was easily induced by nutrient starvation, resuscitation could only be demonstrated following co-incubation of the VBNC cells with the

amoeba An amoeba (; less commonly spelled ameba or amœba; plural ''am(o)ebas'' or ''am(o)ebae'' ), often called an amoeboid, is a type of Cell (biology), cell or unicellular organism with the ability to alter its shape, primarily by extending and ret ...

, ''Acanthamoeba Castellani''" Fungistasis or mycostasis a naturally occurring VBNC (viable but nonculturable) state found in fungi in soil. Watson and Ford defined fungistasis as "when viable fungal propagules, which are not subject to endogenous or constitutive dormancy do not germinate in soil at their favorable temperature or moisture conditions or growth of fungal hyphae is retarded or terminated by conditions of the soil environment other than temperature or moisture". Essentially (and mostly observed naturally occurring in soil) several types of fungi have been found to enter the VBNC state resulting from outside stressors (temperature, available nutrients, oxygen availability etc.) or from no observable stressors at all.

Current research

On March 1, 2018, the

Defense Advanced Research Projects Agency The Defense Advanced Research Projects Agency (DARPA) is a research and development agency of the United States Department of Defense responsible for the development of emerging technologies for use by the military. Originally known as the Adv ...

(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." On March 20, 2018, the Biostasis team held a

Webinar Web conferencing is used as an umbrella term for various types of online conferencing and collaborative services including webinars (web seminars), webcasts, and web meetings. Sometimes it may be used also in the more narrow sense of the peer-le ...

which, along with a

Broad Agency Announcement The Broad Agency Announcement (BAA) is a technique for United States government agencies to solicit proposals from outside groups for certain research and development. The agency will then select proposals to fund as contracts or grants. BAAs are ...

(BAA), solicited five-year research proposals from outside organizations. The full proposals were due on May 22, 2018.

Possible approaches

In their

DARPA The Defense Advanced Research Projects Agency (DARPA) is a research and development agency of the United States Department of Defense responsible for the development of emerging technologies for use by the military. Originally known as the Adv ...

outlined a number of possible research approaches for the Biostasis project. These approaches are based on research into

tardigrade Tardigrades (), known colloquially as water bears or moss piglets, are a phylum of eight-legged segmented micro-animals. They were first described by the German zoologist Johann August Ephraim Goeze in 1773, who called them Kleiner Wasserbär ...

s and

wood frog ''Lithobates sylvaticus'' or ''Rana sylvatica'', commonly known as the wood frog, is a frog species that has a broad distribution over North America, extending from the boreal forest of the north to the southern Appalachians, with several notab ...

s which suggests that selective stabilization of intracellular machinery occurs at the

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

level.

Protein chaperoning

In molecular biology,

molecular chaperones In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assi ...

are proteins that assist in the folding, unfolding, assembly, or disassembly of other

macromolecular A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...

structures. Under typical conditions,

facilitate changes in shape (

conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or oth ...

) of

macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...

s in response to changes in environmental factors like

temperature Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measured with a thermometer. Thermometers are calibrated in various temperature scales that historically have relied o ...

, pH, and

voltage Voltage, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to m ...

. By reducing conformational flexibility, scientists can constrain the function of certain proteins. Recent research has shown that proteins are promiscuous, or able to do jobs in addition to the ones they evolved to carry out. Additionally, protein promiscuity plays a key role in the adaptation of species to new environments. It is possible that finding a way to control

in promiscuous proteins could allow scientists to induce biostasis in living organisms.

Intracellular crowding

The crowdedness of cells is a critical aspect of biological systems. Intracellular crowding refers to the fact that protein function and interaction with water is constrained when the interior of the cell is overcrowded. Intracellular

organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...

s are either membrane-bound vesicles or membrane-less compartments that compartmentalize the cell and enable spatiotemporal control of biological reactions. By introducing these intracellular

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

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 Tardigrades (), known colloquially as water bears or moss piglets, are a phylum of eight-legged segmented micro-animals. They were first described by the German zoologist Johann August Ephraim Goeze in 1773, who called them Kleiner Wasserbär ...

s are

microscopic animals Microfauna (Ancient Greek ''mikros'' "small" + New Latin ''fauna'' "animal") refers to microscopic animals and organisms that exhibit animal-like qualities. Microfauna are represented in the animal kingdom (e.g., nematodes, small arthropods) and t ...

that are able to enter a state of

and survive a remarkable array of environmental stressors, including

freezing Freezing is a phase transition where a liquid turns into a solid when its temperature is lowered below its freezing point. In accordance with the internationally established definition, freezing means the solidification phase change of a liquid o ...

and

desiccation Desiccation () is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic (attracts and holds water) substance that induces or sustains such a state in its local vicinity in a moderately sealed container. ...

. Research has shown that

intrinsically disordered proteins In molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure, typically in the absence of its macromolecular interaction partners, such as other proteins or RNA. IDPs rang ...

in these organisms may work to stabilize cell function and protect against these extreme environmental stressors. By using

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

engineering, it is possible that scientists may be able to introduce

to the biological systems of larger animal organisms. This could allow larger animals to enter a state of biostasis similar to that of

s under extreme biological stress.

References

{{reflist * Oliver, James D. "The viable but nonculturable state in bacteria." ''The Journal of Microbiology'' 43.1 (2005): 93-100. *Fungistasis and general soil biostasis A new synthesis Paolina Garbeva, W.H. Gera Holb, Aad J. Termorshuizenc, George A. Kowalchuka, Wietse de Boer *Watson, A.G., Ford E.J. 1972 Soil Fungistasis—a reappraisal. Annual Review of Phytopathology 10, 327. Ecology Physiology Biology