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Biotechnology Program (BIT)

Dr. Phillip Brown

Research Profile

PB
Dr. Phillip Brown
Phillip Brown

Asst Teaching Professor

919-513-0309

Research Areas:

  • Whole genome sequence analysis
  • Epidemiology
  • Horizontal gene transfer
  • Antimicrobial resistance
  • CRISPR-equipped bacteriophage

Techniques:

  • Molecular cloning
  • DNA-sequencing
  • Graphical interface bioinformatics
  • CRISPR-Cas12a
  • CRISPR-associated transposases

Project Description:

The Centers for Disease Control and Prevention has labelled bacterial antimicrobial resistance (AMR) a global threat [1] due to the consistent increase in yearly AMR-associated human cases [2,3]. AMR is most concerning in six “ESKAPE” bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) due to their role in hospital-acquired infections [4]. However, AMR in non-pathogenic bacteria is also concerning as these bacteria have been shown to be a reservoir for AMR genes, which can be horizontally transferred into human pathogens [5,6]. While being extremely useful traditional antimicrobial compounds are typically non-specific and target a wide range of microbes, including beneficial bacteria, depending on their mechanism of action [7]. The emergence of high throughput sequencing techniques and utilization of CRISPR-Cas systems has allowed for a more specific targeting of bacteria carrying specific genes or sequences [8].

Summer research students will use whole genome sequence data to design CRISPR-Cas systems to combat non-pathogenic antimicrobial resistant bacteria. These CRISPR-Cas systems may target essential genes to directly kill the bacteria, or AMR genes to re-sensitize the bacteria to the corresponding antimicrobial compound. Previous experience in molecular cloning, bioinformatics tools or CRISPR-Cas systems is not necessary, if you are interested in working towards a solution for the AMR crisis or using CRISPR-Cas systems this project is for you.

Get to know Dr. Brown:

What is your research area and why are you passionate about it?

I love looking at the intraspecies interactions of bacteria and how genes can be shared! Strains of the same bacterial species will share a large portion of their genome but they will often also harbor other non-essential genes involved in everything from antibiotic resistance to virulence. Genomic analysis of these accessory genes can be extremely important in understanding how to combat human pathogens.

What do you like most about research?

Science is difficult and working with others who have knowledge you do not can help drive projects forward and help expand your set of skills. I also enjoy feeling like a detective, trying to solve a problem that no one knows the answer to.

How would you describe your mentoring style?

My mentoring style always changes depending on who I am mentoring and what style they prefer or need, I can be either hands off or on. I am always available to answer questions or provide help if students need it but in general I think research is an excellent opportunity for students to become more independent and work through problems.

What is one piece of advice that you would give to students beginning research?

Don’t be afraid to fail. Research experiments rarely work on the first try and troubleshooting is one of the most important skills to learn. If you make a mistake or your experiment does not go as planned don’t panic and don’t be afraid to ask for help.

References:

  1. Centers for Disease Control and Prevention. https://www.cdc.gov/DrugResistance/
  2. Antimicrobial Resistance Collaborators. 2022. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 400:1102. doi: 10.1016/S0140-6736(21)02724-0.
  3. World Health Organization. https://www.who.int/news/item/09-12-2022-report-signals-increasing-resistance-to-antibiotics-in-bacterial-infections-in-humans-and-need-for-better-data
  4. Rice LB. 2008. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis. 197:1079-81. doi: 10.1086/533452.
  5. Poirel L, Madec JY, Lupo A, Schink AK, Kieffer N, Nordmann P, Schwarz S. 2018. Antimicrobial resistance in Escherichia coli. Microbiol Spectr. 6(4). doi: 10.1128/microbiolspec.ARBA-0026-2017.
  6. Soucy SM, Huang J, Gogarten JP. 2015. Horizontal gene transfer: building the web of life. Nat Rev Genet. 16(8):472-82. doi: 10.1038/nrg3962.
  7. Maier L, Goemans CV, Wirbel J, Kuhn M, Eberl C, Pruteanu M, Müller P, Garcia-Santamarina S, Cacace E, Zhang B, Gekeler C, Banerjee T, Anderson EE, Milanese A, Löber U, Forslund SK, Patil KR, Zimmermann M, Stecher B, Zeller G, Bork P, Typas A. 2021. Unravelling the collateral damage of antibiotics on gut bacteria. Nature. 599:120-124. doi: 10.1038/s41586-021-03986-2.
  8. Jiang Y, Chen B, Duan C, Sun B, Yang J, Yang S. 2016. Multigene editing in the Escherichia coli genome via the CRISPR-Cas9 system. Appl Environ Microbiol. 82:3693. doi: 10.1128/AEM.04023-14.