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Conceptually, it is simple to achieve the cell's dream with the following three fundamental processes: the cell duplicates its genetic information (DNA replication), spatially separates the duplicated sets of information (chromosomes segregation) and then divides into two daughter cells.
In bacteria, despite the seeming simplicity of the organism, chromosome segregation is the most mysterious process. Recently, however, we have shown theoretically that duplicating bacterial chromosomes can partition spontaneously to maximize their conformational entropy. This is a strong indication that, with or without protein-based hypothetical “mitotic machinery,” conformational entropy can provide a primordial driving force of segregation for duplicating bacterial chromosomes. A corollary of our results is that, unlike chromsomes, plasmids can readily mix one another because of their small sizes. This suggests that the active segregation mechanism of most low-copy number plasmids (such as R1) might be a product of evolutionary selection.
Below added in January, 2008.
Two main themes of our research revolve around bacteria, especially chromosomes (organization/dynamics/segregation) and “bacteria as individuals.” For this, (1) we have been developing a micro-piston system to study physical properties of chromosomes in an artificial cell environment. This work was motivated by our wish to understand the extent to which the general, fundamental behavior and functioning of chromosomes is governed by their physical and mechanical properties, and (2) we have also constructed a micro chemostat system to link the individuality of bacteria and their behavior as population.
We have a number of (fun) projects available for undergraduate students, which can lead to a publication. Sample projects listed below are designed for students to learn and use a variety of biophysical techniques including, but not limited to: molecular tweezers, single molecule microscopy, microfluidic device fabrication and soft lithography, electrophoresis, and molecular dynamics simulations. Undergraduate students from either the physical and biological sciences are encouraged to apply.
Note. While our lab is always open and happy to discuss, in case you intent to use some of our original ideas, please do contact us first.
1. Micro Pac Man!
We all know the classic game Pac Man. We can adapt this to study the behavior of E.coli in a microfluidic environment. E.coli is a motile bacterium which swims and tumbles to find food. We can design and construct a complex maze and study how geometry influences how E.coli (Pac Man) will swim and search for food. Particle tracking and a fast feedback system will be used. Similarly, we could also use another type of “magnetic” bacterium Magnetospirillum magnetoacticum, which uses a special magnetic compass ‘magnetosome.’ Some programming will be involved.
2. Hydrodynamic trapping of bacteria & Do E.coli love funnels?
The basic question is whether bacteria will be “sucked” towards a surface by hydrodynamic trapping as they should follow curved surfaces. We have made chips with surfaces of different curvatures. Our preliminary results have revealed that bacteria indeed follow the low-curvature surfaces but get off from high-curvature ones. In the literature, elementary theory has been discussed but its quantitative, experimental demonstration has never been reported.
Also, we have designed chips with funneled walls. We are wondering whether the bacteria will move from one place another faster because of the funnels, and we (you!) will watch and quantitatively characterize their motion at individual level in the chips. One particular type of chip is a loop with funnel walls in which the bacteria should go around in one direction.
3. What is the force of growth of bacteria? And for “gliding” bacteria?
We have various tools to immobilize and measure the force of bacteria, and we have two closely-related questions you can work on.
(a) E.coli keeps growing (elongating) as long as they are given nutrients at the right temperature. But how strong is this force of growth? When they face a counter-force against their growth, what will bacteria do?
(b) Mycoplasma mobile is one of the simplest living organisms on earth. It forms membrane projections at the one cell end, attaches to the host cell or glass, and begins to glide! The gliding is performed with special leg-like protein machineries. They grab the material, pull and release it. But how strong is this force of gliding? What is the effect of the difference of grabbing materials? When they face a counter-force against their gliding such as water flow (M. mobile has reotaxis), what will they do? While the very first step of either of these projects is typical of single-molecule force measurement, there is a deeper motivation in the context of evolution to understand how bacteria will respond (if any) when they are in a situation where they cannot do what they are normally supposed to do.
4. Kinetics of “hibernation and waking up” of bacteria – will they “communicate”?
Most bacteria on Earth are hungry. Otherwise, with their ability to multiply exponentially, the planet would already have been taken over by bacteria. As bacteria starve their physiology changes as a protection mechanism. This special energy-saving mode is called the “stationary phase.” We are interested in how bacteria enter the stationary phase and escape from it as their nutrient level changes. This project will involve the fabrication of a micro-chemostat. Various related questions will also be addressed at the individual level.
5. How does a small molecule detect and solve a global, topology problem of the cell?
DNA molecules in a cell almost always feel strong confinement. (For E.coli, the stretched length of its chromosome is 1000 times the size of the cell. In eukaryotic cells, the situation is even worse.) These long molecules are inevitably knotted, which would be devastating if not for the existence of “topoisomerases” (surprise surprise). This is, however, a mind-boggling problem because proteins are small molecules and thus have access to local information only, whereas the chain topology is a global property of the system. Recently, we and other groups have explained why confinement will localize the chain topology (manuscript in preparation), and we are now asking how this confinement-driven localization of chain topology may facilitate topoisomerases’ ability to solve a “math” problem.