Protein conformational diseases (PCDs) are characterized by a progressive loss of neuronal or muscle function due to protein misfolding and aggregation, a common feature among diseases such as Alzheimer’s, Parkinson’s, Huntington’s, or Lou Gehrig’s diseases (ALS). The exact factors that influence PCDs are not known. Recent evidence suggests that bacteria may contribute to the pathogenesis of these neurodegenerative diseases. To better understand the influence of bacteria on protein homeostasis (proteostasis), we are studying the effect of bacterial colonization of the Caenorhabditis elegans gut on protein aggregation in the intestine and other tissues. We found two gram-negative species, Pseudomonas aeruginosa and Klebsiella pneumoniae, that enhanced protein aggregation in the intestine nearly five-fold; these two strains also affect proteostasis across other tissues, including muscle and neurons. Both species can be found as part of the normal human microbiome and are known opportunistic pathogens. An increase in the abundance of these bacteria within the human gut was previously linked with the enhanced progression of neurodegenerative diseases. Collectively, these results suggest that intestinal bacteria affect the host folding environment; however, which bacterial factors are responsible for the enhancement of aggregation remains unknown. Moreover, which bacteria within the entire microbiome enhance or suppress host proteostasis is not known. Our results, along with other published data, demonstrate that butyrogenic bacteria and butyrate suppress protein aggregation and the associated toxicity; however, further work is needed to elicit the exact mechanisms. Collectively, we employ C. elegans to reach the following goals:

(i). Identify bacterial genes that disrupt host proteostasis

(ii). Characterize the effect of the human microbiome bacterial isolates on host proteostasis

(iii). Decipher the mechanisms by which butyrate suppresses bacteria-mediated proteotoxicity

The importance of this project lies in its potential to identify microbial signatures and molecules associated with the pathogenicity of PCDs, thus providing opportunities to develop novel diagnostics, prophylactics, and therapeutics.

Antibiotic resistance is becoming the center of a global healthcare crisis. It is estimated that by 2050, antibiotic resistance will claim ten million lives annually and exert a projected economic burden of $100 trillion. Antibiotics target bacteria, which under high selective pressure, rapidly develop resistance. The overuse of antibiotics in the healthcare and agricultural industries has fueled irreversible resistance to drugs that were once effective in treating common bacterial infections. In addition, the development of novel antibiotics has almost completely ceased. With increasing antibiotic resistance and limited treatment options, bacterial infections are once again becoming intractable, leaving a disastrous socio-economic footprint on humans. While much emphasis has been placed on combating bacteria directly, we have taken a different approach; namely, by targeting the host, rather than the pathogen. Unlike conventional pathogen-targeting antibiotics, this host-targeting strategy can prevent and/or treat infections by:

(i) Modulating uptake of bacteria by phagocytic host cells

(ii) Intercepting host pathways or nutrients utilized by the pathogen during infection

(iii) Enhancing the ability of host cells to kill bacteria

Augmenting the ability of host cells to clear invading bacteria provides a promising strategy. As such, we hypothesize that the host-targeting approach can circumvent antibiotic resistance and provide a powerful tool in the fight against antibiotic resistance. We employ small molecules (drug-repurposing) to enhance the ability of phagocytic immune cells to scavenge, uptake, and kill bacteria, then introduce them into the host either as a prophylactic or therapeutic intervention. Similar cell-based immunotherapy has been successfully applied in cancer treatment, but such a concept has rarely been explored in the area of infectious diseases. The results of our work are expected to have a positive impact on human health because they will spur the development of new treatments for patients who are predisposed to bacterial infections. Moreover, our results will broaden the current understanding of host-pathogen interaction, which can potentially help in the development of additional therapeutics.

The Czyz Research Group explores additional non-traditional approaches to battle AMR. We have isolated unique bacteriophages, viruses that infect and kill bacteria, from the environment. Our cocktail of bacteriophages has a broad-spectrum specificity against about 90% of clinical, environmental, and animal isolates of Pseudomonas aeruginosa. Our laboratory is currently characterizing these phages and exploring their utility in human and animal applications. We just recently launched a clinical trial to test bacteriophages against canine otitis. Furthermore, extensive genomic analysis of phage-resistant strains allowed us to identify genes involved in phage infectivity. We are currently exploring the underlying mechanisms.

Among other non-traditional approaches, the Czyz Lab works on silver nanoparticles (AgNPs) – these metallic particles have potent antimicrobial activity. We explore the antimicrobial mechanisms of AgNPs and their applicability as potential therapeutic. To date, our work revealed that the specific formulation of AgNPs, generated by our collaborator Natural Immunogenics Corporation, can potentiate the efficacy of aminoglycoside antibiotics by over 20-fold. We are currently deciphering the observed synergy. The highly translatable nature of this project can have a significant impact on targeting resistant bacteria and eliminating adverse reactions to aminoglycosides. Our collaboration also explores gold and copper nanoparticles.

This project aims to identify novel antibiotics from bacteria isolated from soil. The majority of clinically important antibiotics have been discovered in bacteria isolated from soil. In fact, more than 70% of all antibiotics come from a single genus of bacteria called Streptomyces. What is more surprising is the fact that only 1-2% of soil bacteria can be cultured under laboratory settings. It is estimated that 0.8-1.6 million unique bacterial species colonize our planet, meaning that the majority of antibiotics used in the clinic come from a small fraction of soil-dwelling bacteria. The early discovery of antibiotics from soil bacteria was attributed to Selman Waksman, a biochemist who discovered more than 20 antibiotics. His approach to screening antibiotics from soil bacteria was termed the Waksman Platform but was soon abandoned due to the availability of effective antibiotics and the high re-discovery rate of already existing antibiotics. An expensive workforce and analytical chemistry techniques combined with the availability of effective antibiotics led to the abandonment of the Waksman Platform. However, with the recent increase in antimicrobial resistance, lack of new antimicrobial developments, and the emergence of new resistance, the need to find and develop novel antibiotics is high. The Czyz group explores -omic approaches to identify novel antibiotics produced by soil-dwelling bacteria. This part of the project is part of the AMR Laboratory course that Dr. Czyz teaches every Fall semester. 

Dr. Czyz teaches two courses on AMR: lecture (MCB5270/MCB4271) and laboratory (MCB4271L). He is also actively involved in fighting AMR outside of his laboratory and class. Dr. Czyz is the past Chair of the Advisory Council at the National Institute of Antimicrobial Resistance Research and Education (NIAMRRE) and continues to be the liaison between the institute and UF.

Admissions and Application Information

The University of Florida Graduate School requires an undergraduate grade point average (GPA) of 3.0 to be eligible for admission. Fulfillment of the minimum requirement does not guarantee an applicant’s acceptance into the program. In evaluating each applicant, the department’s Graduate Committee members include in their consideration a thorough review of the transcript, letters of recommendation, statement of purpose, area of research interest, etc. Students are encouraged to complete undergraduate coursework in biochemistry and microbiology before they apply.

How to Apply

Admission into the UF Microbiology and Cell Science graduate program requires that an applicant be accepted both by the UF Graduate School and by the Microbiology and Cell Science Department. To complete the application process, apply online via the Graduate School admissions web site and select the “Graduate” option to create an account and begin your application. Visit the UF Graduate School web page for step-by-step instructions on how to apply. Select the “Apply Now” icon below to go directly to the Ph.D. Application.

Students are admitted to the PhD program each fall semester. Applications must be completed by December 15th to be considered for admission the following fall semester.

We are not currently accepting applications for the thesis master’s degree program.

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Required Application Materials

• Application fee of $30.
• Official Transcripts.
• CV or resume.
• Three letters of recommendation (LOR). We suggest that candidates request LOR from professional/academic mentors or colleagues that can comment on their academic/research experiences.
• Personal statement. The personal statement should consist of a brief essay describing your research experience, career goals, and area of research interest (limit 500 words)
• Supplemental information. Use this form to provide additional information that will be reviewed by the admissions committee
• International Applicants must also submit TOEFL scores (a score of 23 or higher on the speaking section is required to be considered for admission).
  • TOEFL Score Codes for UF: Institution Code is 5812, Department Code is 07
  • We do not accept the IELTS

Please contact Jacqueline Lee at jlee9@ufl.edu if you have any questions regarding the application process or deadline.