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Principal Investigator: Christian T Meyer
Organization: UNIVERSITY OF COLORADO
Fiscal Year: 2024
Award: $138,699
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Biofilms are intrinsically drug-resistant. While the signaling pathways mediating resistance in biofilms are documented,
only recently has the importance of electrophysiology in modifying gentamicin resistance come to light. However, the role
of electrophysiology in biofilm formation and maturation is unknown. Furthermore, we currently lack high throughput
screening techniques for assessing the bactericidal potential of treatment strategies against clinical biofilms.
During my K99 training, I will investigate how mechanically-stimulated calcium fluctuations modify the c-di-GMP pools
(Aim 1.1) and bacterial swarming (Aim 1.2) leading to biofilm formation. Concomitantly, I will deploy an assay for measur-
ing biofilm viability in high throughput to screen for antibiotic adjuvants against biofilms (Aim 2.1). During this phase, my
training will focus on the culture of biofilms, analysis of non-optical electrophysiology data, and building machine learning
models subsequently applied during my R00 phase.
Following my K99 phase, I will investigate the electrophysiology of mature biofilms using both optical and non-optical
techniques and correlate changes in antibiotic tolerance across the biofilm life-cycle with changes in electrophysiology (Aim
1.3). Concomitantly, I will build and train deep learning models to predict gentamicin adjuvants against slow-growing cells
based on viability data collected in my K99 phase (Aim 2.2).
The product of my project will enrich our understanding of biofilm electrophysiology and enable methods for mitigating
their formation or promoting their retention as is desirable for probiotics. Additionally, this work will deliver new machine
learning technologies for finding antibiotic adjuvants to combat drug-resistant clinical biofilms.
Terms: <Address><Adjuvant><Aminoglycoside resistance><Aminoglycoside resistant><Aminoglycosides><Antibiotic Agents><Antibiotic Drug Combinations><Antibiotic Drugs><Antibiotics><Assay><Bacteria><Basic Research><Basic Science><Bioassay><Biological Assay><Biotech><Biotechnology><COVID-19><CV-19><Calcium><Cell Body><Cell Survival><Cell Viability><Cells><Cessation of life><Chemical Structure><Clinic><Clinical><Combined Antibiotics><Complex><Coronavirus Infectious Disease 2019><DNA Alteration><DNA Replication><DNA Sequence Alteration><DNA Synthesis><DNA biosynthesis><DNA mutation><Data><Death><Development><Drug Combinations><Drug Synergism><Drug resistance><Drugs><Electrophysiology><Electrophysiology (science)><Garamicin><Garamycin><Gene Combinations><Generalized Growth><Genetic mutation><Genoptic><Genoptic S.O.P.><Gentamicins><Growth><High Throughput Assay><Hospitals><Infection><Intervention><Intervention Strategies><Life Cycle><Life Cycle Stages><Machine Learning><Measurement><Measures><Mechanical Stimulation><Mechanics><Mediating><Medication><Metabolic><Methods><Microbial Biofilms><Miscellaneous Antibiotic><Morphology><Motility><Neurophysiology / Electrophysiology><Optics><Outcome><Pharmaceutical Preparations><Phase><Physiologic><Physiological><Physiology><Position><Positioning Attribute><Postdoc><Postdoctoral Fellow><Predictive Value><Probiotics><Refractory><Research Associate><Resistance><Role><Sequence Alteration><Signal Pathway><Speed><Suspension substance><Suspensions><Techniques><Technology><Testing><Therapeutic><Tissue Growth><Training><U-Gencin><Urinary tract infection><Urinary tract infectious disease><Work><antibiotic resistant infections><antibiotic resistant pathogen><antibiotic tolerance><bactericidal><bactericide><biofilm><combat><combinatorial><commune><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><curse of dimensionality><data to train><dataset to train><deep learning><deep learning based model><deep learning method><deep learning model><deep learning strategy><density><developmental><drug resistant><drug resistant pathogen><drug/agent><electrophysiological><genomic alteration><high throughput screening><in silico><innovate><innovation><innovative><insight><interventional strategy><invention><knockout gene><life course><machine based learning><machine learning based model><machine learning model><mechanic><mechanical><minimal inhibitory concentration><multi-electrode arrays><multielectrode arrays><new drug combination><new pharmacotherapy combination><new technology><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><new treatment approach><new treatment strategy><non-genetic><nongenetic><novel drug combination><novel pharmacotherapy combination><novel technologies><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapy approach><ontogeny><optical><post-doc><post-doctoral><post-doctoral trainee><pre-clinical><preclinical><preempt><research associates><resistance to Drug><resistance to aminoglycoside><resistant><resistant to Drug><resistant to aminoglycoside><screening><screenings><sensor><social role><soft tissue><synergism><tech development><technology development><tolerance to antibiotics><tolerate antibiotics><training data><treatment strategy><urinary infection>