Tweet<\/a><\/p>\n The question of where we have come from has fascinated\u2014and frustrated\u2014intellectuals of all sorts, for centuries. There have therefore been experiments in several learned disciplines to investigate this problem. Between them, they have produced lots of answers to the question. One such discipline is cell biology. The question in this context is how a newly born human baby, a viable multi-cellular organism, can form from just one cell. A human live birth at full term comprises about 716 billion cells. This means that cell division produces an average of 2.6 billion cells per day of the pregnancy. It is hard to imagine that\u2014but the number itslef is not that important: all we need to know for these purposes is that it is a lot.<\/p>\n Unfortunately, there are analogous and far less happy examples of cellular growth at this speed. Cancers typically start with a mutation in a single cell, forming one that typically divides so rapidly and without a means to stop it, that it can overwhelm the system in which it lives. The system of controlling cell division, and thus the cell cycle, has got lost, been turned off or been inhibited out of use. Both systems containing cancers, and healthy ones that do not have been researched by cell biologists, with a view to determining how their cell cycles are controlled.<\/p>\n The work of Sir Paul Nurse<\/a> and Sir Tim Hunt<\/a> (described on the and in a BBC documentary<\/a> established the way the cell cycle is controlled in eukaryotes. It is controlled by changes in gene expression, by changes in the concentration of proteins called cyclins.<\/p>\n I first heard about this in 2010, when I was writing my PhD thesis. This was years after the Nobel prize has been awarded in 2001 and therefore longer still after it had been published. This sat in my mind until about two years ago, when I was researching E. coli<\/em> for a quite different purpose. I stumbled upon evidence that there are no analogues of cyclins in bacteria, and that gene expression does not change in bacteria during the cell cycle [1]. What interested me about this work was that the question of what was<\/em> controlling the cell cycle.<\/p>\n I looked into other details of the system. For example, structural proteins are made and assemble into a sort of internal scaffold that supports the physical process of division. However, their concentration does not change through the cell cycle, so it is not reasonable to think they are at the centre of controlling the cycle either [2].<\/p>\n One possibility, I thought, was a fundamental of the process. In order for a cell to divide, it must grow longer (elongate) in order that the two cells produced are large enough to be viable. This means that the cell envelope\u2014the system comprising the cell membrane\u2014must increase in size by a factor of two before division. So, at the very least, the membrane limits the rate of cell division. I developed the hypothesis that it controls it, too.<\/p>\n The principal component of the membrane is the lipid fraction. There are proteins as well, some of which produce lipids, but ultimately most of the membrane\u2019s area is lipids. This means that in order for the cell to divide, a big effort in making lipids is required. This is simplified in E. coli<\/em> because it comprises only about 4 major lipid components. One of these, phosphatidic acid (PA), typically represents less than 1% of the total and is thus often ignored. Another component, phosphatidylethanolamine (PE) often represents more than 80% of the total and thus dominates. Of the two remaining, phosphatidyl glycerol (PG) is the principal substrate for making cardolipin (CL).<\/p>\n Furthermore, evidence about how these lipids are spread out through the membrane, has been researched and reported. There is evidence from studies where cells were dyed that CL is found at the ends (poles) of the cells. This meant that when cells were elongated, the percentage of CL would be lower. This is because the poles have stayed at the same size but the middle of the cell is longer. This offered the tantalising hypothesis that the cell might control its lipid profile, only producing CL when it made new poles, for example during division.<\/p>\n We therefore tested the hypothesis that the lipid profile of E. coli<\/em> changes through the cell cycle. The next obvious question to answer, if such a study was to take place, was how this should be done. We elected to arrest the cells in two of the three periods of the cell cycle, the resting state and the state in which they are at their most elongated. The lipid profile was determined at each (See figure). The results were that the CL fraction fell in the way we expected, but also that the PG fraction increased a lot. In fact, there was a higher percentage of PG in the elongated cells than in the ones in the resting state. This suggested that the rate of its production was faster than that of the cell\u2019s elongation [3].<\/p>\n