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Post-Doc Fellowship Awarded to Melinda Grosser

Melinda Grosser in her lab.

AHA Post-Doc Fellowship

Melinda Grosser has been awarded an American Heart Association (AHA) Post-Doc Fellowship that will fund her research for two years. Dr. Grosser is a member of Berkeley Optometry professor Suzanne Fleiszig’s lab.

Research Goals

Communities of bacteria called biofilms are common in human infections. Biofilm bacteria produce a matrix of carbohydrates, DNA and proteins that facilitates adherence to surfaces and provides physical protection. As a result, biofilms are highly resistant to antibiotics and the immune response. However, individual constituents of matrices and their roles in biofilm integrity are unclear. Dr. Grosser’s research will address the problem of how Pseudomonas aeruginosa, a bacterial species that forms biofilms on contact lenses, holds its biofilms together on contact lenses during wear. P. aeruginosa is among the most common causes of bacterial keratitis, a potentially blinding corneal disease associated with contact lens wear. One of Dr. Grosser’s hypotheses is that an adhesive biofilm matrix protein called CdrA is central to the ability of P. aeruginosa to maintain intact biofilms on contact lenses, ultimately leading to corneal infection. Dr. Grosser will investigate how contact lens biofilms are affected by exposure to the tear film and ocular surface in the presence and absence of CdrA.

Potential Outcomes

Biofilm matrix components are promising drug targets, but we must first realize the roles of each component and how its targeting will impact disease. Dr. Grosser’s results will define the importance of the matrix protein CdrA to P. aeruginosa persistence in biofilms on contact lenses. This will inform further experiments that could lead to treatments to disrupt biofilm matrices, with implications for preventing and treating contact lens-associated infections.

In addition to its significance for contact lens-related infections, this work is important to the AHA because P. aeruginosa biofilms are common on cardiovascular devices such as intravenous catheters, cardiac pacemakers, and ventricular assist devices, leading to chronic infections. Studying biofilms on cardiovascular devices can be difficult in mouse models because they are highly invasive. Dr. Grosser’s study will use contact lenses as model noninvasive indwelling medical devices to learn general information about the contributions of biofilm matrix components to tissue infection. Further, because the device and infected tissue are transparent, the contact lens model uniquely allows for performance of high resolution imaging throughout biofilm development.

Bacteria on contact lens and cornea

In vivo confocal image of P. aeruginosa on a mouse contact lens and cornea with cdrA transcriptional reporter. All bacteria exhibit constitutive blue fluorescence for identification. A cdrA transcriptional fusion with gfp shows that cdrA, encoding an important biofilm matrix protein, is heterogeneously expressed after 4 h of contact lens wear on a mouse eye. (Photo credit: Melinda Grosser and Matteo Metruccio)