Research

Where Microbiology and Chemistry Intersecta "wordcloud" representation of recent activity in our lab. . .
As this tagcloud representing a summary of several recent publications from my lab indicates, my research resides at intersections of microbiology and chemistry.  I am a broadly trained microbiologist with expertise applying state-of-the-art approaches, particularly in proteomics and functional genomics to: 1) leverage  beneficial aspects of microorganisms (e.g., biodegradation/ bioremediation of harmful chemical pollutants) and 2) develop approaches to mitigate negative effects of microorganisms (e.g., disease, microbial contamination of water).  Most recently, my research group has placed considerable focus on the development and optimization of rapid, mass spectrometry-enabled approaches to characterize microorganisms at the strain level.








Of Microbes and Metals. . .

Microorganisms exhibit remarkable metabolic diversity.  This diversity can be exploited in the design of strategies to clean up (bioremediate) hazardous wastes in the environment.  Unfortunately, many hazardous waste sites that contain pollutants that microorganisms can degrade also contain toxic metals that impinge upon the ability of microorganisms to clean up (biodegrade) pollutants.  For this reason, my research group has explored strategies to increase the efficacy of bioremediation of metal-contaminated environments.  We have explored through functional genomics-based approaches basic mechanisms by which metal toxicity is mediated by environmental pH.  As shown in the dendrogram at right, environmental pH affects microbial responses to metals at the level of the genome.

As shown in the three figures below, we've applied knowledge we've learned about metal toxicity to mitigate metal toxicity during hydrocarbon (naphthalene) biodegradation.  Figures below show that a modified cyclodextrin (carboxymethly beta-cyclodextrin) reduces metal toxicity during naphthalene biodegradation in the presence of toxic cadmium (A), cobalt (B), and copper (C).




Even Microbes Have Fingerprints: Microbial Profiling using Molecular- and Rapid, Proteomics-based Approaches

In other projects, we have been utilizing genetic fingerprinting (rep-PCR) to characterize environmental isolates of E. coli found contaminating recreational waters.  The top left panel below shows DNA fingerprints of about 38 E. coli isolates, while the MDS plot below shows the similarity in 3-d space of many such DNA fingerprints.


Given the time-intensive nature of PCR-based fingerprinting methods, we have developed very rapid, mass spectrometry-based methods to characterize microorganisms including E. coli and Enterococcus.  The top image below shows a simplified, overview of this approach, while the dendrogram below shows the similarity of fingerprints of several E. coli isolates from different environmental sources.  















While recently applying this rapid approach to a variety of bacteria, we noticed that the commonly employed practice of automating data acquisition reduced spectrum quality and reproducibility.  The panel below shows the reproducibility of replicate spectra of 8 different bacteria (each shown in a different color) in 3-dimensional space (via a multidimensional scaling, MDS, representation of the data) for spectra acquired by automation (panel A), an experienced human MALDI operator (panel B), and a less experienced human MALDI operator (panel C).  As is clear from these panels, both human operators obtained spectra that exhibited higher reproducibility than spectra obtained by automation.





Given this discovery, we have employed a designed experiments approach to optimize automated data acquisition of MALDI spectra. The animation shown at right highlights one of our first successes with P. aeruginosa. Green spheres represent replicate spectra obtained with optimization, while red spheres represent replicate spectra obtained without optimization.











We describe further our success optimizing automated data acquisition in one of our most recent publications (Zhang L, Borror CM, Sandrin TR. 2014.  A designed experiments approach to optimization of automated data acquisition during characterization of bacteria with MALDI-TOF mass spectrometry.  PLoS ONE. DOI: 10.1371/journal.pone.0092720).  Spectra of P. aeruginosa acquired without optimization (top spectrum) and with optimization (bottom spectrum) are shown below.  Our approach was successful not only with P. aeruginosa (A), but also with two other Gram-negative bacteria, K. pneumoniae (B) and S. marcescens (C).  Spectra obtained using optimized settings are represented by green spheres in the MDS plots below.



  

Antimicrobial resistant microorganisms pose a serious threat to human health.  Recently, we optimized spectrum processing parameters to enhance the ability of rapid, MS-based microbial fingerprinting to detect antibiotic-resistance in 172 strains of the food- and waterborne pathogen, Campylobacter, obtained from across four continents.  As shown in the panels below, beta-lactam resistant strains (red spheres) were more readily discriminated from susceptible strains (green spheres) when default processing parameters (A) were optimized (B).


Publications, many of which resulted from the work described above, include the following. (Undergraduate student collaborators are designated with an *, while graduate student collaborators are designated with a **. Post-doctoral collaborators are designated with a §). 

Journal Articles:

  • Sandrin TR, Demirev PA. 2017. Characterization of microbial mixtures by mass spectrometry. Mass Spectrometry Reviews.  May 16.

  • Penny C, Grothendick B*, Zhang L§, Borror CM, Barbano D**, Cornelius, AJ, Gilpin BJ, Fagerquist CK, Zaragoza WJ, Jay-Russell MT, Lastovica AJ, Ragimbeau C, Cauchie HM, Sandrin TR.  2016. A designed experiments approach to optimizing MALDI-TOF MS spectrum processing parameters enhances detection of antibiotic resistance in Campylobacter jejuni. Front. Microbiol. doi: 10.3389/fmicb.2016.00818.

  • Zhang L, Smart S*, Sandrin TR. 2015. Biomarker-and similarity coefficient-based approaches to bacterial mixture characterization using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Scientific Reports 5: 15834.

  • Barbano D**, Diaz R*, Zhang L§, Sandrin TR, Gerken H, Dempster T.  2015. Rapid Characterization of Microalgae and Microalgae Mixtures Using Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS). PLoS ONE  DOI:10.1371/journal.pone.0135337.

  • Zhang L§, Vranckx K, Janssens K, Sandrin TR. 2015. Use of MALDI-TOF mass spectrometry and custom databases to characterize bacteria indigenous to a unique cave environment (Kartchner Caverns, AZ, USA). Invited Contribution. Journal of Visualized Experiments (JoVE) 95: e52064. DOI: 10.3791/52064.

  • Zhang L§, Borror CM, Sandrin TR. 2014.  A designed experiments approach to optimization of automated data acquisition during characterization of bacteria with MALDI-TOF mass spectrometry.  PLoS ONE. DOI: 10.1371/journal.pone.0092720
  • Goldstein JE*, Zhang L, Borror CM, Rago JV, Sandrin TR2013. Culture conditions and sample preparation methods affect spectrum quality and reproducibility during profiling of Staphylococcus aureus with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.  Letters in Applied Microbiology. 57(2): 144-150.


  • Sandrin TR, Goldstein JE*, Schumaker S*. 2013. MALDI TOF MS Profiling of bacteria at the strain level: A review. Mass Spectrometry Reviews 32:188-217. (cover of issue in which article appeared is shown at right)







  • Schumaker S*, Borror C, Sandrin TR. 2012. Automating data acquisition affects mass spectrum quality and reproducibility during bacterial profiling using an intact cell sample preparation method with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry.  26(3): 243-253.
  • Badgley  BD, Ferguson J, Vanden Heuvel A*, Kleinheinz GT, McDermott CM,  Sandrin TR, Kinzleman J, Junion EA, Byappanahalli MN, Whitman RL, and Sadowsky MJ. 2011. ­Multi-scale temporal and spatial variation in genotypic composition of Cladophora-borne E. coli populations in Lake Michigan. Water Research. 45(2): 721-31.
  • Vanden Heuvel A*, McDermott C,  Pillsbury R, Sandrin TR, Kinzelman J, Ferguson J, Sadowsky M, Byappanahalli M, Whitman R., Kleinheinz GT.  2010. The green alga, Cladophora, promotes E. coli growth and contamination of recreational waters in Lake Michigan.  Journal of Environmental Quality 39: 333-34.
  • Giebel R, Worden C, Rust S*, Kleinheinz GT, Robbins M*, Sandrin TR. 2010.  Microbial fingerprinting using Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS):  Applications and challenges. Invited contribution.  Advances in Applied Microbiology71:149-84.
  • Hoffman DR**, Anderson PP*, Schubert CM*, Gault MB*, Blanford WJ, Sandrin TR. 2010. Carboxymethyl-β-cyclodextrin mitigates toxicity of cadmium, cobalt, and copper during naphthalene biodegradation. Bioresource Technology. 2672-77.
  • Worden CR**, Kovac W*, Dorn L, Sandrin TR.  2009. Environmental pH affects transcriptional responses to cadmium toxicity in Escherichia coli K-12 (MG1655). FEMS Microbiology Letters. 293(1): 58-64.
  • Giebel R**, Fredenberg W*, Sandrin, TR. 2008. Characterization of environmental strains of Enterococcus sp. using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF-MS). Water Research 42: 931-940.
  • Siegrist TJ**, Anderson PD*, Huen WH, Kleinheinz GT, McDermott CM, Sandrin TR. 2007. Discrimination and characterization of environmental strains of Escherichia coli by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF-MS). Journal of Microbiological Methods 68(3): 554-562.
  • Grandlic CJ**, Geib I*, Pilon R*, Sandrin TR. 2006. Lead pollution in a large, prairie-pothole lake (Rush Lake, WI, USA): Effects on abundance and community structure of indigenous sediment bacteria. Environmental Pollution. 144(1): 119-126.
  • Sandrin TR, Kight WB, Maier WJ, and Maier RM. 2006. Influence of a nonaqueous phase liquid (NAPL) on biodegradation of phenanthrene. Biodegradation 17(5): 423-435.
  • Hoffman DR**, Okon JL*, and Sandrin TR. 2005. Medium composition affects degrees and patterns of cadmium inhibition of naphthalene biodegradation. Chemosphere. 59(7): 919-927.
  • Sandrin TR, TeBeest D.O., Weidemann GJ. 2003. Soybean and sunflower oils increase the infectivity of Colletotrichum gloeosporioides f. sp. aeschynomene to northern jointvetch. Journal of Biological Control 26:244-252.
  • Al-Tahhan R., Sandrin TR, Bodour AA, Maier RM. 2000. Rhamnolipid-Induced removal of lipopolysaccharide from Pseudomonas aeruginosa: Effect on cell surface properties and interaction with hydrophobic substrates. Applied and Environmental Microbiology 66: 3262-3268.
Patents
  • Sandrin TR, Jurutka P. US Provisional Application No. 61/943,739. Gene expression based biomarker system for Irritable Bowel Syndrome (IBS) diagnosis. Filed 2/25/2015. 
News/Other Press



Books:
Book Chapters:

  • Zhang L, Sandrin TR. 2015. Maximizing the taxonomic resolution of MALDI-TOF-MS-based approaches to bacterial characterization:  From culture conditions through data analysis. In Applications of Mass Spectrometry in Microbiology: From Strain Characterization to Rapid Screening for Antibiotic Resistance. Demirev P, Sandrin T. Springer

  • Worden CR**, Kleinheinz GT, Sandrin TR. 2010. Effects of Heavy Metals on Microorganisms in the Environment.  Invited contribution.  Handbook of Advanced Industrial and Hazardous Wastes Treatment.  Wang LK, Hung YT, Shammas NK, Eds. CRC Press. pp. 409-428.
  • Sandrin TR, Herman D, Maier R.  2009.  Chapter 11: Physiological Methods.  In Environmental Microbiology. 2nd ed. Academic Press: San Diego, CA. 
  • Dowd S, Herman D, Sandrin TR, Maier R. 2009. Chapter 6: Aquatic and Extreme Environments. In Environmental Microbiology. 2nd ed.  Academic Press: San Diego, CA.  
  • Sandrin TR, Hoffman DR**. 2007. Bioremediation of Organic and Metal Co-contaminated Environments: Effects of Metal Toxicity, Speciation, and Bioavailability on Biodegradation.  Invited contribution. Environmental Bioremediation Technologies. Singh SN and Tripathi RD, eds. pp. 1-34. Springer-Verlag: Berlin.  
  • Sandrin TR. 2004. Bioremediation of Exxon Valdez: A Case Study. Invited Contribution. In Microbiology. Cowan and Talaro. McGraw-Hill: Boston. 1st edition.

Scholarship of Teaching and Learning

  • Sandrin TR and Ledwell B. 2004. Regulation of Biosynthesis: Attenuation of the trp operon. American Society for Microbiology - Microbe library. http://www.microbelibrary.org.

  • Sandrin TR and Ledwell B. 2003. Regulation ofEnzyme Activity: Allosterism. American Society for Microbiology - Microbe library.  http://www.microbelibrary.org/
     
  • Sandrin TR and Ledwell B. 2003. Rho-dependentTermination of Transcription. American Society for Microbiology - Microbe Library. http://www.microbelibrary.org/

  • Sandrin TR. 2003. An Animation of TranscriptionalRegulation in Bacteria: Negative Regulation. American Society for Microbiology - Microbe Library. http://www.microbelibrary.org/

  • Sandrin TR. 2003. An Animation of TranscriptionalRegulation in Bacteria: Positive Regulation. American Society for Microbiology - Microbe Library.  http://www.microbelibrary.org/

Some Recent and Forthcoming Presentations
  • Imig K*, Enow JA*, Born K*, Scholz-Ng S*, Reissig M*, Tidgwell A*, Truscott A*, De Young A*, Barrett R*, Gutierrez A*, Tuohy J*, Mueller-Spitz S*, Sandrin T.  2016. Use of protein extraction mass spectrometry for rapid determination of phylogenetic relationships of Deinococcus aquaticus isolates obtained from biofilm samples.  Community College Undergraduate Research Initiative (CCURI) Colloquium. Glendale Community College. Glendale, AZ. Nov. 29.

  • Sandrin TR, Gutierrez A*. 2016.  Applications of mass spectrometry in microbiology: From strain characterization to rapid screening for antibiotic resistance.  Glendale Community College Biotechnology Research Seminar Series. September 30.  

  • Barbano D**, Gutierrez*, Sandrin TR. 2016. Growth phase affects MALDI-TOF Mass Spectra of Chlorella vulgaris cultures.  American Society for Microbiology (ASM) Arizona-Southern Nevada Branch Annual Meeting. April 16. 

  • Penny C, Zhang L, Grothendick B*, Fagerquist CK, Zaragoza WJ, Miller WG, Ragimbeau C, Mossong J, Cornelius AJ, Gilpin BJ, On SLW, Cauchie HM, Sandrin TR. 2015. Subspecies typing of environmental and human health-related Campylobacter jejuni strains using MALDI-TOF mass spectrometry.  18th International workshop on Campylobacter, Helicobacter and Related Organisms. Rotorua, New Zealand. Nov. 1-5. 

  • Dempster TA, Gerken H, Barbano D**, Diaz R*, Zhang L, Sandrin TR. 2015. MALDI-TOF MS as a tool for taxonomic discrimination and identification of economically significant microalgae strains.  5th International Conference on Algal Biomass, Biofuels, and Bioproducts.  San Diego. June 7-10.   

  • Sandrin TR, Zhang L, Grothendick B*, Barbano D**, Diaz R*, Borror CM, Gerken H, Dempster T. 2015.  Maximizing the performance of MALDI-TOF-MS-based microbial characterization: From culture conditions through data analysis.  29th Indian Society for Mass Spectrometry (ISMAS) International Symposium on Mass Spectrometry. Jodhpur, India. Invited Oral Presentation. February 2-6.

  •  Sandrin TR, Zhang L, Borror CM, Grothendick B*. 2015.  Maximizing the taxonomic resolution of MALDI-TOF-MS-based approaches to bacterial characterization: Implications for rapid detection of antibiotic resistance. 1st International Caparica Conference in Antibiotic Resistance. Caparica, Portugal. Invited Oral Presentation. January 26-28.

  •  Schwake DO**, Sandrin TR, Zhang L, Abbaszadegan M. 2014.  Strain-level characterization of environmental isolates of Legionella via MALDI-TOF MS.  American Water Works Association Water Quality Technology Conference. November 19.

  • Grothendick B*, Zhang L, Sandrin TR. 2014. Mass spectrum processing parameters affect strain-level MALDI-TOF MS-based characterization of Paenibacillus larvae isolates.  Annual Meeting of the Arizona-Nevada Academy of Science.  Apr. 12.

  • Dussik CM*, Hockley MM*, Sabir MS*, Kaneko I, Zhang L, Galligan MA, Sandrin TR, Jurutka PJ.  2014. Identification of differentially expressed genes as biomarkers for diagnosis of irritable bowel syndrome (IBS). Annual Meeting of the Arizona-Nevada Academy of Science.  Apr. 12. 

  • Sandrin TR. 2014. From the beach to bees: Using mass spectrometry to rapidly characterize bacteria at the species level and beyond. University of Nevada Las Vegas. School of Life Sciences Seminar Series. Invited Oral Presentation. February 6, 2014.
  • Hockley MM*, Galligan MA, Zhang L, Sandrin TR, Jurutka PW. 2013. Identification of differentially expressed genes as biomarkers for diagnosis of Irritable Bowel Syndrome (IBS): A pilot gene discovery hypothesis generating study. Joint Annual Meeting of the Pacific Division of the American Association for the Advancement of Science (AAAS) and the Arizona-Nevada Academy of Science (ANAS).  June 16-19.  

  • Sandrin TR. 2013.  Culture conditions and sample preparation affect spectrum quality, reproducibility, and characterization of methicillin resistance during MALDI-TOF-MS-based profiling of methicillin resistant and methicillin sensitive Staphylococcus aureus (MRSA and MSSA).  Invited Oral Presentation. Annual Meeting of the American Society for Microbiology.  Denver, CO. May 21.

  • Sandrin TR. 2013.  Rapid, mass spectrometry-enabled characterization of environmentally-relevant bacteria: From microbial water quality indicators to MRSA.  Invited Oral Presentation52nd Annual Meeting of the Arizona/Southern Nevada Branch of the American Society for Microbiology.  Tucson, AZ.  April 13.

  • Schumaker S*, Borror C, Zhang L, Sandrin T. 2013.  A designed experiments-based approach to optimization of automated data acquisition during characterization of Pseudomonas aeruginosa with Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). 52nd Annual Meeting of the Arizona/Southern Nevada Branch of the American Society for Microbiology.  Tucson, AZ.  April 13.
     
  • Zhang L, Schumaker S*, Sandrin T.  2013.  MALDI-TOF mass spectrometry as a rapid tool for characterization of bacteria indigenous to Kartchner Caverns, AZ .  52nd Annual Meeting of the Arizona/Southern Nevada Branch of the American Society for Microbiology.  Tucson, AZ.  April 13.

  • Smith P*, Spence J*, Zhang L, Sandrin T. 2013.  Effect of target surface type and sample preparation protocol on spectrum quality and reproducibility during bacterial characterization using MALDI-TOF MS.  52nd Annual Meeting of the Arizona/Southern Nevada Branch of the American Society for Microbiology.  Tucson, AZ.  April 13. P. Smith received a Poster Award for this presentation.
     
  • Hockley MM*, Galligan MA, Zhang L, Sandrin TR, Jurutka PW. 2013. Identification of Differentially expressed genes as biomarkers for diagnosis of Irritable Bowel Syndrome (IBS): A pilot gene discovery hypothesis generating study. Open Door @ ASU West. March 2. Contribution: co-mentored undergraduate student; microarray data analysis.

  • Sandrin TR, Borror CB. 2012. Assessment of automated data acquisition and its effects on bacterial profiling. 29th Annual Quality and Productivity Research Conference. Invited Program. San Diego, CA. June 6.

  • Sandrin TR. 2012. Advances in the application of MALDI-TOF-MS-based fingerprinting to the characterization of waterborne microorganisms: successes, challenges, and strategies for the future.  Invited Keynote Address.  Workshop on MALDI-TOF MS Applications for Microbial Identification and Characterization. Centre de Recherche Public – Gabriel Lippmann.  Belavux, Luxembourg. May 16.
     
  • Goldstein J*, Sandrin TR. 2012. Culture conditions and sample preparation affect quality and reproducibility of spectra obtained from methicillin-resistant Staphylococcus aureus (MRSA) using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS).  Proceedings of the Arizona-Nevada Academy of Science.  Apr. 14. Goldstein awarded 1st place/Best Oral Presentation Award.
     
  • Sandrin TR. 2011. NCUIRE-ing Minds Want to Know: Does providing tiered research opportunities broaden and increase participation in undergraduate research? Gateways to Best Practices for Undergraduate Research Program Directors Conference. Council on Undergraduate Research. Washington University.  St. Louis, Missouri. June 14-16.
     
  • Schumaker S*, Rust S*, Sandrin TR. 2011. Man(ual) versus machine in microbial fingerprinting using MALDI-TOF-MS: Effect of automating data acquisition on fingerprint reproducibility and quality.  New College Undergraduate Student Research and Creative Projects Expo. April 21.

  • Moreno F*, Davidov E*, Nguyen N**, Sandrin TR. 2011.  Effect of medium type on the diversity and abundance of heterotrophic microorganisms recovered from Kartchner Caverns (Benson, AZ). New College Undergraduate Student Research and Creative Projects Expo. April 21.

  • Goldstein J*, Murray D*, Chidester A*, Richholt R*, Sandrin TR. 2011.  Differential Analysis and Bacterial Fingerprinting of Wild Type and Transformed E. coli using MALDI-TOF MS.  Proceedings of the Arizona-Nevada Academy of Science.  Apr. 9.  Contribution: mentored undergraduate co-authors in use of MALDI-TOF MS.

  • Schumaker S*, Rust S*, Nguyen N, Sandrin TR. 2011.  Man(ual) versus Machine in Microbial Fingerprinting using MALDI-TOF-MS: Effect of Automating Data Acquisition on Fingerprint Reproducibility and Quality.   Proceedings of the Arizona-Nevada Academy of Science. Apr. 9.

  • Rust S*, Sandrin TR. 2010.  Quantifying reproducibility of microbial fingerprinting using MALDI-TOF-MS: Effect of automating data acquisition.  New College of Interdisciplinary Arts and Sciences Spring Expo.  Rust was awarded 3rd place award.

  • Rust S*, Sandrin TR. 2010.  Quantifying reproducibility of microbial fingerprinting using MALDI-TOF-MS: Effect of automating data acquisition Annual Meeting of the Arizona-Nevada Academy of Science. Apr. 10.

  • Nguyen N, Henderson A*, Sandrin TR. 2010.  Are difficult-to-culture microorganisms more hungry or lonely?  Application of a tissue culture insert (TCI)-based approach to cultivating microorganisms indigenous to Kartchner Caverns, Arizona.  Annual Meeting of the Arizona-Nevada Academy of Science. Apr. 10. 

If you are interested in getting involved in any of these projects or are interested in any kind of research in microbiology and/or environmental science, contact me via email or stop by my office (FAB N106C or FAB N303B) or lab (CLCC 311).



Support for some work shown here has been supported, in part, by the following:


https://www.srpnet.com/

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