Faculty Profile: Hochbaum, Allon
|Faculty Information||Lab Information (Packet Type, Course Title, & Department)||Location|
Department: Molecular Biology and Biochemistry
The ability to respond to stressful and changing conditions is a critical requirement for bacterial survival in any environment. Types of stress that bacteria cope with are wide ranging: heat, acid/base, desiccation, oxidative, osmotic, nutrient (e.g. carbon, nitrogen, phosphorous) deprivation, oxygen/oxidant deprivation, stress from antimicrobial compounds, heavy metals, surfactants and other sources. In the Hochbaum lab, we are interested in stresses associated with bacterial infection - chemical interactions with the host and other commensal or pathogenic microbes, stresses associated with biofilm formation like osmotic stress and nutrient/oxygen deprivation, and stress responses and susceptibility to therapies such as antibiotic treatment.
For example, one set of current projects involves the use of spectroscopic methods to detect antibiotic susceptibility in clinical infections:
Antibiotic susceptibility testing (AST) is an integral tool for combating the growing problem of antibiotic resistant bacteria. Conventional AST methods use growth-based assays that require 24-72 h for results. Shortening the time to AST results to 30-60 min would minimize prescription of ineffective antibiotics, improving antibiotic stewardship and patient outcomes. Metabolomic analyses of the effects of antibiotics suggest that a common mechanism of killing in bacteria is a systemic dysregulation of metabolic activity that occurs within 30 min of exposure. Consequently, methods for rapidly assessing changes in bacterial metabolic state represent a promising approach to AST. In the Hochbaum lab, we are currently developing three approaches to rapid AST - (1) spectroscopic microscopy to measure metabolic rate with single-cell resolution and the ability to map metabolic activity in 3D (useful for looking at physiological changes in biofilms); (2) combining Raman spectroscopy with machine learning approaches to rapidly classify metabolic states of cells exposed to antibiotics; (3) fluorimetric assays of metabolic activity for high throughput (with robots!) identification of effective antimicrobial therapies. Since metabolic changes occur much faster than variations in gene expression in response to stress, our central hypothesis is that new methods for characterizing these shifts in metabolite profiles at very short times can be useful for a number of biomedical and industrial applications.
More fundamentally, we are interested in using the above metabolomic methods to generate functional classifications of stress responses based on their effects on bacterial metabolic function. Projects along these lines include work to (1) functionally classify antibiotics by their metabolic consequences rather than targets in the cell and (2) identifying mechanisms of cooperatively between biosurfactants and signaling molecules or antimicrobial compounds. These efforts lay the groundwork for the development of cell-based sensors of their surroundings. Since bacteria already have multiple systems for sensing and responding to their local environment, if we can reliably read out these changes and distinguish their metabolic consequences, we can use bacterial cultures as living sensors for analytes ranging from (i) arsenic and other toxic heavy metals to (ii) human-derived factors characteristic of performance or health, and (iii) subtle changes in growth medium formulations that affect the yields of various biotechnology processes.
Many of these projects require conventional microbiological, molecular biology, and analytical chemistry methods to validate and provide insight into the outputs of new techniques being developed in lab. As a result, no prior microbiology experience is necessary. New students will be trained in standard sterile culture methods, growth and killing assays, and various analytical methods as the projects dictate. As you, a new student, progress in your abilities and conceptual understanding of the project, you will have the opportunity to design experiments using advanced quantitative techniques and even develop new methods for gaining insight into interesting biological questions.
Several research efforts in lab are in the process of commercialization, so students interested in working in translational science are also encouraged to apply.
Please get in contact with Prof. Hochbaum to set a time to discuss your research interests, the lab's current needs, and potential opportunities for research.
Requirements to Participate
An interest in bacterial metabolism, quantitative analysis methods, and asking important biological questions. Former undergrads in the lab have gone on to top graduate schools, Fulbright and domestic research fellowships, and research positions in industry. New members are expected to bring a strong work ethic, a commitment to rigorous and creative lab work, and to be prepared for collaborative and highly interdisciplinary research. 3 - 4 hours per unit.
1 year Commitment.
Minimum 2 units.
Faculty Means of Evaluation
Attendance: 20% (working committed hours, being on time, attending lab meetings)
Lab work: 40% (attention to detail, quality, accuracy and reproducibility of work, data analysis and designing experiments)
Communication: 20% (Written/oral reports, questions and discussion with mentor)
Lab citizenship: 20% (working safely, organized work space, clean up of work space and shared equipment and space, follow through on responsibilities)