Biology subjects

Kurzchalia, T. V.

Publications and source records attributed to Kurzchalia, T. V..

4 recordsLinked to original sources

bioRxiv2022

Nematodes can survive in a suspended form of life for indefinite time

Some organisms in nature have developed the ability to enter a state of suspended metabolism called cryptobiosis1 when environmental conditions are unfavorable. This state-transition requires execution of a combination of genetic and biochemical pathways1,2,3 that enable the organism to survive for prolonged periods. Recently, nematode individuals have been reanimated from Siberian permafrost after remaining in cryptobiosis. Preliminary analysis indicates that these nematodes belong to the genera Panagrolaimus and Plectus4. Here, we present precise radiocarbon dating indicating that the Panagrolaimus individuals have remained in cryptobiosis since the late Pleistocene ([~]46,000 years). Phylogenetic inference based on our genome assembly and a detailed morphological analysis demonstrate that they belong to an undescribed species, which we named Panagrolaimus n. sp. Comparative genome analysis revealed that the molecular toolkit for cryptobiosis in Panagrolaimus n. sp. and in C. elegans is partly orthologous. We show that biochemical mechanisms employed by these two species to survive desiccation and freezing under laboratory conditions are similar. Our experimental evidence also reveals that C. elegans dauer larvae can remain viable for longer periods in suspended animation than previously reported. Altogether, our findings demonstrate that nematodes evolved mechanisms potentially allowing them to suspend life over geological time scales.

genomics↗

bioRxiv2021

Periodic ethanol supply as a path towards unlimited lifespan of C.elegans dauer larvae

The dauer larva is a specialized stage of development optimized for survival under harsh conditions that has been used as a model for stress resistance, metabolic adaptations, and longevity. Recent findings suggest that the dauer larva of C.elegans may utilize external ethanol as an energy source to extend their lifespan. It was shown that while ethanol may serve as an effectively infinite source of energy, some toxic compounds accumulating as byproducts of its metabolism may lead to the damage of mitochondria and thus limit the lifespan of larvae. A minimal mathematical model was proposed to explain the connection between the lifespan of dauer larva and its ethanol metabolism. To explore theoretically if it is possible to extend even further the lifespan of dauer larvae, we incorporated two natural mechanisms describing the recovery of damaged mitochondria and elimination of toxic compounds, which were previously omitted in the model. Numerical simulations of the revised model suggest that while the ethanol concentration is constant, the lifespan still stays limited. However, if ethanol is supplied periodically, with a suitable frequency and amplitude, the dauer could survive as long as we observe the system. Analytical methods further help to explain how the feeding frequency and amplitude affect the lifespan extension. Based on comparison of the model with experimental data for fixed ethanol concentration, we propose the range of feeding protocols that could lead to even longer dauer survival and can be tested experimentally.

biophysics↗

bioRxiv2021

Quantitative imaging of Caenorhabditis elegans dauer larvae during cryptobiotic transition using optical diffraction tomography

Upon starvation or overcrowding, the nematode Caenorhabditis elegans enters diapause by forming a dauer larva. This larva can further transit into an anhydrobiotic state and survive harsh desiccation. We previously identified the genetic and biochemical pathways essential for survival -- but without an accompanying physical model, the mechanistic understanding of this amazing phenomenon will remain inadequate. Neither microscopic investigation of structural changes upon entry into anhydrobiosis nor the most basic quantitative characterization of material properties of living desiccated larvae, however, have been feasible, due to lack of appropriate techniques. Here, we employed optical diffraction tomography (ODT) to quantitatively assess the internal mass density distribution of living larvae in the reproductive and diapause stages. More importantly, ODT allowed for the first time physical analysis of desiccated dauer larvae: their mass density was significantly increased in the anhydrobiotic state. We also applied ODT on different mutants that are sensitive to desiccation. Remarkably, one of them displayed structural abnormalities in the anhydrobiotic stage that could not be observed either by conventional light or electron microscopy. Our advance opens a door to quantitatively assessing fine differences in material properties and structure necessary to fully understanding an organism on the verge of life and death.

biophysics↗

bioRxiv2018

An insulin, AMPK, and steroid hormone-mediated metabolic switch regulates the transition between growth and diapause in C. elegans

The balance between growth and quiescence depends on the global metabolic state. The dauer larva of C. elegans, a developmentally arrested stage for survival under adverse environment, undergoes a major metabolic transition. Here, we show that this switch involves the concerted activity of several regulatory pathways. Whereas the steroid hormone receptor DAF-12 controls dauer morphogenesis, the insulin pathway maintains low energy expenditure through DAF-16/FoxO, which also requires AAK-2/AMPK. DAF-12 and AAK-2 separately promote a shift in the molar ratios between competing enzymes at two key branch points within the central carbon metabolic pathway. This way, carbon atoms are diverted from the TCA cycle and directed to gluconeogenesis. When both AAK-2 and DAF-12 are suppressed, the TCA cycle is active and the developmental arrest is bypassed. Hence, the metabolic status of each developmental stage is defined by stoichiometric ratios within the constellation of metabolic enzymes and controls the transition between growth and quiescence.

biochemistry↗