Honors & Awards


  • Dean's Fellowship, Stanford School of Medicine (2017-2018)

Professional Education


  • Bachelor of Science, University of Massachusetts Amherst (2009)
  • Doctor of Philosophy, California Institute of Technology (2016)

Stanford Advisors


Lab Affiliations


All Publications


  • SutA is a bacterial transcription factor expressed during slow growth in Pseudomonas aeruginosa PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Babin, B. M., Bergkessel, M., Sweredoski, M. J., Moradian, A., Hess, S., Newman, D. K., Tirrell, D. A. 2016; 113 (5): E597-E605

    Abstract

    Microbial quiescence and slow growth are ubiquitous physiological states, but their study is complicated by low levels of metabolic activity. To address this issue, we used a time-selective proteome-labeling method [bioorthogonal noncanonical amino acid tagging (BONCAT)] to identify proteins synthesized preferentially, but at extremely low rates, under anaerobic survival conditions by the opportunistic pathogen Pseudomonas aeruginosa. One of these proteins is a transcriptional regulator that has no homology to any characterized protein domains and is posttranscriptionally up-regulated during survival and slow growth. This small, acidic protein associates with RNA polymerase, and chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing suggests that the protein associates with genomic DNA through this interaction. ChIP signal is found both in promoter regions and throughout the coding sequences of many genes and is particularly enriched at ribosomal protein genes and in the promoter regions of rRNA genes. Deletion of the gene encoding this protein affects expression of these and many other genes and impacts biofilm formation, secondary metabolite production, and fitness in fluctuating conditions. On the basis of these observations, we have designated the protein SutA (survival under transitions A).

    View details for DOI 10.1073/pnas.1514412113

    View details for Web of Science ID 000369085100016

    View details for PubMedID 26787849

    View details for PubMedCentralID PMC4747698

  • In situ visualization of newly synthesized proteins in environmental microbes using amino acid tagging and click chemistry ENVIRONMENTAL MICROBIOLOGY Hatzenpichler, R., Scheller, S., Tavormina, P. L., Babin, B. M., Tirrell, D. A., Orphan, V. J. 2014; 16 (8): 2568-2590

    Abstract

    Here we describe the application of a new click chemistry method for fluorescent tracking of protein synthesis in individual microorganisms within environmental samples. This technique, termed bioorthogonal non-canonical amino acid tagging (BONCAT), is based on the in vivo incorporation of the non-canonical amino acid L-azidohomoalanine (AHA), a surrogate for l-methionine, followed by fluorescent labelling of AHA-containing cellular proteins by azide-alkyne click chemistry. BONCAT was evaluated with a range of phylogenetically and physiologically diverse archaeal and bacterial pure cultures and enrichments, and used to visualize translationally active cells within complex environmental samples including an oral biofilm, freshwater and anoxic sediment. We also developed combined assays that couple BONCAT with ribosomal RNA (rRNA)-targeted fluorescence in situ hybridization (FISH), enabling a direct link between taxonomic identity and translational activity. Using a methanotrophic enrichment culture incubated under different conditions, we demonstrate the potential of BONCAT-FISH to study microbial physiology in situ. A direct comparison of anabolic activity using BONCAT and stable isotope labelling by nano-scale secondary ion mass spectrometry ((15)NH(3) assimilation) for individual cells within a sediment-sourced enrichment culture showed concordance between AHA-positive cells and (15)N enrichment. BONCAT-FISH offers a fast, inexpensive and straightforward fluorescence microscopy method for studying the in situ activity of environmental microbes on a single-cell level.

    View details for DOI 10.1111/1462-2920.12436

    View details for Web of Science ID 000340522500017

    View details for PubMedID 24571640

    View details for PubMedCentralID PMC4122687

  • State-selective Metabolic Labeling of Cellular Proteins ACS CHEMICAL BIOLOGY Ngo, J. T., Babin, B. M., Champion, J. A., Schuman, E. M., Tirrell, D. A. 2012; 7 (8): 1326-1330

    Abstract

    Transcriptional activity from a specified promoter can provide a useful marker for the physiological state of a cell. Here we introduce a method for selective tagging of proteins made in cells in which specified promoters are active. Tagged proteins can be modified with affinity reagents for enrichment or with fluorescent dyes for visualization. The method allows state-selective analysis of the proteome, whereby proteins synthesized in predetermined physiological states can be identified. The approach is demonstrated by proteome-wide labeling of bacterial proteins upon activation of the P(BAD) promoter and the SoxRS regulon and provides a basis for analysis of more complex systems including spatially heterogeneous microbial cultures and biofilms.

    View details for DOI 10.1021/cb300238w

    View details for Web of Science ID 000307526600003

    View details for PubMedID 22692961

    View details for PubMedCentralID PMC3423470

  • Noninvasive characterization of in situ forming implants using diagnostic ultrasound JOURNAL OF CONTROLLED RELEASE Solorio, L., Babin, B. M., Patel, R. B., Mach, J., Azar, N., Exner, A. A. 2010; 143 (2): 183-190

    Abstract

    In situ forming drug delivery systems provide a means by which a controlled release depot can be physically inserted into a target site without the use of surgery. The release rate of drugs from these systems is often related to the rate of implant formation. Currently, only a limited number of techniques are available to monitor phase inversion, and none of these methods can be used to visualize the process directly and noninvasively. In this study, diagnostic ultrasound was used to visualize and quantify the process of implant formation in a phase inversion based system both in vitro and in vivo. Concurrently, sodium fluorescein was used as a mock drug to evaluate the drug release profiles and correlate drug release and implant formation processes. Implants comprised of three different molecular weight poly(lactic-co-glycolic acid) (PLGA) polymers dissolved in 1-methyl-2-pyrrolidinone (NMP) were studied in vitro and a 29 kDa PLGA solution was evaluated in vivo. The implants were encapsulated in a 1% agarose tissue phantom for five days, or injected into a rat subcutaneously and evaluated for 48 h. Quantitative measurements of the gray-scale value (corresponding to the rate of implant formation), swelling, and precipitation were evaluated using image analysis techniques, showing that polymer molecular weight has a considerable effect on the swelling and formation of the in situ drug delivery depots. A linear correlation was also seen between the in vivo release and depot formation (R(2)=0.93). This study demonstrates, for the first time, that ultrasound can be used to noninvasively and nondestructively monitor and evaluate the phase inversion process of in situ forming drug delivery implants, and that the formation process can be directly related to the initial phase of drug release dependent on this formation.

    View details for DOI 10.1016/j.jconrel.2010.01.001

    View details for Web of Science ID 000277219200004

    View details for PubMedID 20060859

    View details for PubMedCentralID PMC2847659

  • A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics LAB ON A CHIP Walsh, C. L., Babin, B. M., Kasinskas, R. W., Foster, J. A., McGarry, M. J., Forbes, N. S. 2009; 9 (4): 545-554

    Abstract

    The heterogeneity of cellular microenvironments in tumors severely limits the efficacy of most cancer therapies. We have designed a microfluidic device that mimics the microenvironment gradients present in tumors that will enable the development of more effective cancer therapies. Tumor cell masses were formed within micron-scale chambers exposed to medium perfusion on one side to create linear nutrient gradients. The optical accessibility of the PDMS and glass device enables quantitative transmitted and fluorescence microscopy of all regions of the cell masses. Time-lapse microscopy was used to measure the growth rate and show that the device can be used for long-term efficacy studies. Fluorescence microscopy was used to demonstrate that the cell mass contained viable, apoptotic, and acidic regions similar to in vivo tumors. The diffusion coefficient of doxorubicin was accurately measured, and the accumulation of therapeutic bacteria was quantified. The device is simple to construct, and it can easily be reproduced to create an array of in vitro tumors. Because microenvironment gradients and penetration play critical roles controlling drug efficacy, we believe that this microfluidic device will be vital for understanding the behavior of common cancer drugs in solid tumors and designing novel intratumorally targeted therapeutics.

    View details for DOI 10.1039/b810571e

    View details for Web of Science ID 000263465900007

    View details for PubMedID 19190790

    View details for PubMedCentralID PMC2855303