Uncovers the determinants of bacterial size and deduces a new "individual growth split equation"

On May 18, the international authoritative academic journal Nature Microbiology published an article by Liu Chenli Laboratory of the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences and the Institute of Synthetic Biology Innovation of Shenzhen, which "The General Quantitative Relationship between E. coli cell growth and cell cycle", which uses E. coli as a model organism, debunks the determinants of bacterial size, deduces a new "individual growth and division equation", corrects the two original growth rules in the field, and provides a basis for the rational design of life in the field of synthetic biology.
bacteria, is the most widely distributed in nature, the largest number of individual single-celled living organisms.
from lactic acid bacteria responsible for fermenting yogurt to E. coli, which produces insulin, bacteria are infested with every aspect of human life and scientific research.
each bacterium has a wide range of inherited sizes, and these tiny cells can sometimes vary by 106-108 times in size, from mycoplasma, a specialist intracellular source of 0.3 micro-meters long, to the 600-micro-tailed symbiotic bacteria Epulopiscium fishelsoni, which grows on the Namibian coast.
of course, the larger bacteria are very rare, most of which are known to be between 0.4 and 2 microns in diameter and between 0.5 and 5 microns in length.
bacteria are not only diverse, but also stable.
bacterial cells in these environments remain edion at a certain size, even in hydrothermal vents with temperatures of more than 100 degrees above temperature, salt lakes with concentrations of up to 5 moles, and radioactive intensity of ions 1,000 times greater than the lethal dose of humans.
, the size of bacteria has long been an indispensable feature in bacterial taxonomy, and a specific size makes bacteria more adaptable to their living environment.
for the past 100 years, biologists have wondered what determines the size of cells.
in modern times, although we know most of the molecules that control bacterial cell cycles and cell division, we still don't know how the size of bacterial cells is determined (Figure 1). On May 18,
, the international authoritative academic journal Nature Microbiology published an article by Liu Chenli Laboratory of the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences and the Institute of Synthetic Biology Innovation of the Chinese Academy of Sciences, "The General Quantitative Relationship linking E. coli cell growth and cell cycle", which, with E. coli as a model organism, revealed the determinants of bacterial size, deduced a new "individual growth and division equation", and corrected the two original growth laws in the field of biological life.
tracing the original law back to the 1950s, American scientists such as Schaechter found that the faster bacterial cells grow, the larger the cells.
more importantly, the study used a mathematical formula to describe the quantitative relationship between the growth rate of bacterial cells and the size of cells, that is, knowing that cells grow slowly, you can accurately infer the size of the cells, and vice versa.
this formula is called the "SMK Growth Law".
, why is there such a relationship between cell size and growth rate? In 1968, Donachie published his opinion in the journal Nature.
he believes that cell size determines when DNA within cells begins a new round of replication.
the ratio of cell size to the number of replication starting points is constant as cells enter the replication phase.
this ratio is called the "starting mass" and the "starting mass" is independent of the growth rate.
begina with a new round of DNA replication, after a constant time period, the cells divide.
because cells are exponentially grown and the starting mass and time period are constant, the size of the cells is proportional to the exponential sub-index of the growth rate when divided.
this view fits well with the SMK growth law, which answers the basic scientific question of "how bacteria size is determined", known as the "constant starting mass hypothesis".
a three-year long study of the two growth laws that have dominated academia for half a century, like the "road signs" on the road of scientific research, in this field to establish authority for sixdecade years, over the years many studies under the guidance of the two laws;
in order to correct the mainstream cell growth law, it is necessary to ensure the complete coverage of experimental data and a high degree of repeatability, Liu Chenli team dedicated more than 3 years of research, the two major laws of systematic repeated experiments.
"The usual study of this kind of study selected 1 or a few kinds of media, and we selected more than 30 kinds of media to carry out experiments, we use morning and evening shift system, the growth of the cell in real-time monitoring to ensure that each sampling is carried out in a stable state of the cell," said Dr. Zheng Hai, the first author of the article.
"This is the most widely used medium-based type of medium and the widest range of growth rates ever reported in similar studies."
with great patience and rigorous attitude, the team finally found that the original two laws are not accurate, as the classic "road sign" may lead everyone's research to the direction of deviation.
"Although the faster the growth speed, the larger the cell, but the relationship between the two does not meet the expectations of the SMK growth law," said Liu Chenli, the paper's communications author, "according to the law, regardless of the fast growth of cells, once the 'starting mass' should be achieved, a new round of DNA replication should begin, however, we observed in the experiment that bacterial cells did not follow the hypothesis, different culture conditions, 'starting quality' has a high and low."
"If the two rules are not accurate, how does the size of the bacteria determine?" Can we correct the "road sign"? Play data to deduce a new quantitative relationship in order to answer the scientific question "How bacteria size is determined," Liu Chenli describes the process of experimental data analysis: "Stay with the data and figure it out."
" the research team, by looking for the quantitative relationship behind a large amount of scientific data, eventually introduced a new "individual growth division equation" that applies to different growth rate conditions (Figure 2): the new equation unified the bacterial cell cycle regulation mechanism under different growth rates, and this quantitative formula also makes natural phenomena such as individual bacterial size and growth rate have some predictability, for example, when the growth rate and replication cycle of bacteria can be accurately predicted.
this division equation provides researchers with a new research paradigm and way of thinking, and answers the relationship between bacterial cell size and DNA replication cycle and growth rate, and has a wide range of applications. what does
"individual growth equation" mean for understanding the control mechanisms of bacterial cell cycles? Under the constraintof the "individual growth equation", the research team discussed the control mechanism of bacterial cell division.
and this based on a new molecular mechanism hypothesis, the existence of a "split license", it is related to "cell growth" and "chromosome replication separation."
when it accumulates to a certain threshold, the cells divide.
the research team based on the establishment of the corresponding mathematical model, further experiments do verify the theoretical prediction.
from mathematical formula to construct the rational design of life body in the physical world, "Bernoulli equation" guides the design of aircraft, "Archimedbuoya's floating force law" promotes the introduction of submarines, "Newton's second law" is the theoretical cornerstone of human space, the ultimate goal of synthetic biology is to realize the biological world rational design, transformation of existing life forms or create new life forms to meet the different needs of human beings.
with "synthetic biology" as the research-oriented, Liu Chenli team after last year revealed the bacterial population migration formula, the study is a breakthrough in the field of quantitative biology, "the study once again confirmed the importance of quantitative thinking methods in life science research, we find every operating law, are trying to find can guide the design, transformation, reconstruction of life forms of 'drawings'."
," Liu said.
this research on the basic scientific problems of the quantitative laws and laws of individual bacterial cells provides an important reference for human stoicism to reveal and understand the principles of life in the body, and this research also contributes to the rational design and construction of the field of synthetic biology in the future to meet the needs of bacteria in the treatment of diseases, antibiotic substitution, green biology manufacturing and other applications.
Source: Voice of the Chinese Academy of Sciences.