Dr. Liraz's background combines both chemistry and biology. This duality of expertise gave birth to a very exciting research of bacterial biofilms, which are communities of bacterial cells that grow on both natural and synthetic surfaces. Biofilms can be beneficial as in the case of protecting plant roots from pathogens. However, they’re mostly considered harmful and related to many bacterial infections. For example, when they develop on catheters or in the lungs of Cystic Fibrosis patients or any other artificial implant in the human body, they most likely lead to death. Biofilms can contribute to serious diseases, like in the case of many hospital acquired infections (HAIs); a group of diseases that have rapidly becoming a leading cause of death in USA and all over the world. Moreover, bacterial biofilms may cause serious economical issues in some industries. For example, in the desalination industry, replacing biofilm-covered pipes and filters is rather costly.
According to Liraz: “A biofilm is a network or aggregates of bacterial cells, held together by a matrix of large macromolecules. What’s interesting for us is investigating the extracellular matrix which is crucial for the development and survival of these biofilms. The extracellular matrix is this mesh of biopolymers, mainly polysaccharides, proteins and nucleic acids that connects the biofilm’s cells together. We are studying this 3D network, its composition, its structure and the intermolecular forces holding the macromolecules together within the matrix”.
The reason why these networks are important to investigate is because they protect the cells from antibiotics thereby increasing their resistance to toxins and antibiotics compared to the form of individual cells. Understanding these networks could be promising in different aspects, for example in designing new drugs that may help increasing the efficacy of antibiotics.
“We’re trying to look at the extracellular matrix as a whole and in parallel to characterize the composition of individual components. Regardless of the fact that it’s basically composed of proteins and polysaccharides, their exact molecular composition and structure in and outside the biofilm context are still not very well known”, explains Liraz.
It’s known that the bacterial cells are not in direct contact to each other but are held together by the extracellular matrix. Studying these interactions not only inside the whole macromolecular network but also between fragments, the basic building blocks for this network, will lead to successful design of molecules which have the ability to interrupt and/ or prevent the formation of the bacterial biofilm. In the Chai lab, they don’t aim to kill the bacterial cells as others do in conventional approaches. “Since these bacterial biofilms are robust and resistant to extreme conditions, adds Dr. Chai, this won’t help getting rid of them. Instead, we want to find a way to keep the bacteria in the form of single cells and inhibit them from sticking to each other, to disrupt the building of the network. We believe that we can achieve this by addressing this main research question; how biofilms are exactly formed and what are the basic physical rules that govern their formation? This will eventually enable us to engineer and develop specific molecules that would interfere with the extracellular matrix and thus disrupt the formation of these extensive biofilms. This has a great impact as it will make it much easier and more efficient to treat bacterial infections with lower doses of antibiotics and/ or for shorter periods; that’s our approach”.
On the other hand, sometimes we aim to do exactly the opposite, i.e. to design molecules that can promote the formation of beneficial bacterial biofilms, like those formed by the Bacillus Subtilis, which live in the soil, attached to the plants’ roots, and is known to be able to tolerate extreme environmental conditions and protect the plants from pathogens by forming biofilms. That’s actually another aspect of Chai’s research.
In fact, the extracellular matrix can induce the formation of minerals, mainly calcium carbonate which can be used in more applicative aspects. For example, such bacterial matrices can be used to fill in the holes in concrete; they form biofilms and fill the gaps in between by calcification, if the environment is convenient; a little bit of moisture can help. In addition, we try to understand how the bacteria is involved in the kidney stones formation by investigating in how the extracellular matrix is related to the precipitation of calcium oxalate, which is the mineral that precipitate in the kidney and causes upon crystallization the formation of kidney stones.
Dr. Chai’s research team is dedicated to addressing all these issues which require not only extensive research in the lab, but also intensive use of the facilities of the nanocenter, more specifically the unit for nanocharacterization (UNC). For example, they use the cryogenic transmission electron microscope (Cryo-TEM) to characterize the biofilm structure, more specifically the protein fibers. They also utilize the scanning electron microscope (SEM), the powder X-ray diffraction (XRD) and the Thermo-gravimetric analysis (TGA) to characterize the crystal structure formed upon mineralization. This nanocharacteriaztion is crucial for this field, Liraz says. “Our nanocenter is amazing, and it serves our research a lot. The equipment is state of the art and the technicians operating it are highly professional and very dedicated and my research highly depends on them. I hope that in the future they could have more specialized tools for imaging biological samples. Biological sample preparation and imaging would make our nanocenter even with world-class nanocenters and would promote my research significantly”.