Nick Lane

nick.lane@ucl.ac.uk

NICK LANE RESEARCH INTERESTS

My main interest is evolutionary biochemistry and bioenergetics, and specifically the process of chemiosmosis, through which cells generate energy in the form of ATP by way of a proton gradient across a membrane. Called ‘the most counter-intuitive idea in biology since Darwin’, the mechanism of chemiosmosis has been elucidated at atomic resolution, yet its evolutionary significance has received little attention.

My research focuses on three major transitions in evolution: the origin of life itself; the origin of the eukaryotic cell; and the evolution of fundamental traits shared by all eukaryotic cells, in particular sexes, speciation and senescence. I am framing a new hypothesis that chemiosmosis played a critical role in each transition.

The origin of life

Hypothesis: natural proton gradients powered the origin of life

On thermodynamic grounds, chemiosmotic coupling was strictly necessary for the origin of life – chemical coupling does not provide sufficient energy to power any chemoautotrophic metabolism. Alkaline hydrothermal vents provide natural proton gradients, with the correct polarity and a similar membrane potential to living cells, potentially explaining why proton gradients are universal across life.

My research concerns the ways in which proton gradients could be harnessed abiotically to power the emergence of biochemical pathways from geochemistry. High-pressure through-flow reactors simulating alkaline vent conditions can help resolve specific questions, notably whether phosphate cycles to pyrophosphate (PPi) under a pH gradient; whether PPi can drive primordial biochemistry by phosphorylating simple organics like acetate, in the same way as ATP; and whether mineral composition influences the relations between Mg2+, Ca2+, Fe2+, Pi and simple organics (which also act as chelators) in primordial biochemistry.

The origin of the eukaryotic cell

Hypothesis: control of chemiosmosis by endosymbiotic genome outposts enabled eukaryotic complexity

All complex life on earth is eukaryotic. The eukaryotic cell arose from prokaryotes just once in 4 billion years, by way of a rare endosymbiosis between two prokaryotes. By controlling chemiosmosis across a wide area of internal membranes, the reduced endosymbiont genomes enabled a vast leap in the host cell’s volume and genome size, which underpinned eukaryotic genome complexity and the origin of complex life.

My research concerns the bioenergetic relationships between the endosymbiont and the host cell, addressed theoretically by comparative bioenergetics and genomics, by modelling of the selection pressures involved in gene transfer, and experimentally by simulating the metabolic syntrophies between prokaryotes in an effort to engineer proto-eukaryotic cells. Experimental questions include addressing the metabolic profiles of cells under varying selection conditions in culture flasks; attempting to engineer cybrids between methanogens and a-proteobacteria; and determining patterns of endosymbiotic gene transfer, protein expression, size, shape and metabolic capability of single cells and cybrids.

The evolution of basal eukaryotic traits

Hypothesis: selection for mitonuclear coadaptation is the basis of sex, speciation and senescence

Complex eukaryotic cells cannot exist without highly reduced mitochondrial genomes, but the requirement for interaction between nuclear and mitochondrial genomes means that they must coadapt for cells to survive. Yet intriguingly, the two genomes differ radically in both tempo and mode of evolution. Some of the most basic eukaryotic traits, including sex, speciation and senescence may be a consequence of the need to coadapt genomes.

My research concerns the strength of selection acting on cells and organisms with mildly mis-matched mitochondrial and nuclear genomes, by modelling the likelihood of apoptosis during embryonic development with or without uniparental inheritance of mitochondria, asking whether such selection pressures are strong enough to overcome the two-fold cost of sex; and whether hybrid breakdown in outcrosses might account for Haldane’s law and speciation. The possible role of mitochondrial mismatch in aging allows experimental investigation of the relationship between ROS leak, membrane potential, apoptosis and mitochondrial biogenesis, using confocal microscopy and fluorescence imaging.