- How do cytoskeletal proteins control cell shape and division in different microorganisms?
- Which signals and stresses are key to instigating change?
- What structural changes correlate with various environmental changes?
- Can we control or prevent pathogenic bacteria taking a form that promotes their survival during infection?
Microbes are ubiquitous and consequently have evolved to exist in a variety of conditions that range in temperature, pH, salinity, and oxygen availability. These include the salt lake dweller Haloferax volcanii, Escherichia coli, a gut microbe that is associated with urinary tract infections, and Helicobacter pylori, known for its role in stomach inflammation, ulcers and cancer.
Microorganisms can be characterised by their predominant shape, for example, spherical, rod-shaped, or spiral – although some can quickly morph in response to environmental changes. Changing their shape can help them survive when faced with threats such as antibiotics, immune reactions, and nutrient-poor surroundings. To do this, cells must alter the structure of their envelope. Guiding this process is the cytoskeleton, an internal structure that establishes the spatial arrangement of the cell and its parts.
Cytoskeletons are made of proteins that assemble into nano-scale fibres or mesh-like structures. A feature common to most cytoskeletal proteins is nucleotide (GTP/ATP) binding and hydrolysis (breakdown), which regulates the assembly or disassembly of the cytoskeleton. In response to external stimuli, cells are able to change the cytoskeleton and modify their envelope structure and stability to help them survive under different conditions.
In human cells, the predominant cytoskeletal proteins are actin and tubulin. Although microorganisms have many of the same essential proteins as humans, including several related to actin and tubulin, studying similarities and differences between species can yield greater insight into the role and regulation of these molecules as well as evolutionary insight. For example, H. volcanii is from a major branch of the tree of life called Archaea. The archaea are a distinct group of microorganisms, often found in extremely harsh environments, so they are metabolically diverse and contain very stable proteins that may have novel industrial applications. As a model organism, H. volcanii is well suited to laboratory studies and microscopy; their cells are amenable to genetic modification and are relatively large and flat. In many archaea, a tubulin-like protein called FtsZ controls pision; whereas one called CetZ specifically regulates archaeal cell shape (see publications for further information). An actin-like protein (MreB) helps direct the shape of the cell envelope in bacteria.
Regulation of the cell envelope structure and growth by cytoskeletal proteins is also important for the survival of bacteria that cause infectious diseases. A striking example is the morphological response of E. coli during urinary tract infection. These normally rod-shaped bacteria stop dividing and grow into very long fibre-like cells, called bacterial filaments. This helps the bacteria colonize surfaces of the urinary tract and withstand an attack by the host’s immune system. We are investigating the molecular triggers and regulation of filamentation and its reversal to reform rod-shaped E. coli.
We are also working on novel cytoskeletal proteins from H. pylori, which are thought to be involved in stress survival in the stomach.
Research focus: Cell cycle and cell structural responses to change and stress and function and regulation of cytoskeletal proteins
Tags: Archaea, Cell cycle, Cell pision, Cell division, Cell shape, Cytoskeleton, H. pylori, H. volcanii, Replication, Stress response, uropathogenic E. coli, morphogenesis, filamentation
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