Research Focus: Prof. R Lewis, Newcastle University

Today we’re talking to Prof. Rick Lewis about his lab’s recent research article just published in Nature Communications, titled “Structure and function of a spectrin-like regulator of bacterial cytokinesis.”  Rick is a specialist in structural biology, with his lab being based within Newcastle University’s Institute for Cell and Molecular Biology (ICaMB).

AS: First, we’d love to hear a bit more about the focus of your lab:

RL:  My lab is interested in how bacteria build a protective coat, called the cell wall, and how the synthesis of the coat is co-ordinated with growth of the cell and with cell division. Take, for example, the rod-shaped bacterium Bacillus subtilis. For many decades, this organism has been the subject of intensive study to understand many generic principles of microbiology, such as the challenge outlined above. A new B. subtilis cell grows until it is twice as long, at which point the cell divides in half, a process that is driven by the constriction of a belt that runs all the way around the middle of the cell. Once the belt has closed completely, cell division is over and the two new cells grow in length, and when they are twice as long, the division process proceeds again, and this phenomenon continues ad infinitum. At the same time, the cell must also make an identical copy of its genome so that the new cell has its own copy of the genetic code.

AS:  With that in mind, how does your recent journal article fit in with this?

RL:  A key protein in the contractile belt is FtsZ; in eukaryotes, the equivalent protein is called tubulin. About 15 years ago, Jan Löwe’s group solved the structure of FtsZ, demonstrating that tubulin had evolved from a bacterial ancestor. FtsZ/tubulin proteins are part of the cytoskeleton of the cell, a protein layer beneath the cytoplasmic membrane that helps provide mechanical strength and shape. It is imperative for the healthy cell to co-ordinate the contraction of the belt (also known as the Z-ring), with cell division, the copying of the genome and the other activities of the cytoskeleton.

A key regulator of FtsZ is EzrA, structures of which we have recently solved using the macromolecular crystallography beamlines at Diamond and the Australian Synchrotron as part of a collaboration with colleagues in Australia. The structure of EzrA comprises five copies of an unusual structural motif, a triple helical bundle, arranged in a linear array to form a complete semi-circle. The repeating units of EzrA, and their linear organisation, are similar to other eukaryotic cytoskeletal proteins called the spectrins. These proteins link the cytoskeleton to the cell membrane, a function that is replicated by EzrA. With respect to the cell membrane, EzrA is arranged much like a hoop through which individual strands of the Z-ring can pass. Z-ring contraction is regulated by EzrA’s unique structure; the hooped structure means that individual strands of the Z-ring cannot associate with neighbouring strands. Since it is the sliding of one strand against another that drives contraction, the hooped structure of EzrA is an effective means to regulate this process.

4-press-release

AS:  So what is the next step for this work?  Where are you hoping this research will lead?

RL: Our glimpse into the fascinating world of bacterial cell division regulators is a story briefly told, and the next step, though beyond the current study, is to understand how EzrA regulates the contraction of the Z-ring by determining structures of EzrA in complex with FtsZ and other cytoskeletal proteins.

AS: Any last words?

RL: The work described could not have been completed if it were not for our continued access to the world-class facilities at Diamond and the Australian Synchrotron, and, of course, the dedication of some brilliant and hard-working co-workers and collaborators.

 

So there you have it, a role for EzrA in the regulation of bacterial cell division.  We would like to say a big thank you to Rick for his time.  If you enjoyed this introduction, then go and read the paper!

 

If you would like your work to be featured on our next Research Focus, then drop us an email at antisensescience@gmail.com.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s