January 12, 2018 kmclaughlin

Research

In the McLaughlin Lab we are committed to creating and maintaining a diverse, inclusive, and accessible training environment within our laboratory, department, and the Vassar College Community. 

Additionally in Fall 2018, Prof. McLaughlin started an undergraduate STEM student group called the Alliance for Diversity Science and Engineering (ADSE) to support students here at Vassar, particularly students who are underrepresented in the STEM fields. Our undergraduate ADSE chapter is part of a national non-profit student run organization dedicated to building an inclusive and diverse community. Most ADSE chapters are for graduate students, however Vassar is home to one of only two undergraduate ADSE chapters in the country.

If you are interested in learning more about ADSE or about the projects/lab (after reading the research summaries below!), contact Dr. McLaughlin at kmclaughlin@vassar.edu.

Lab Publications (full list): NCBI Bibliography

Research Overview

We often think about bacteria only in the context of an infection, however the majority of bacteria we interact with are harmless- with many living symbiotically in/on us as part of the human microbiome. In the human gut alone there are more that 1200 different species of bacteria which help us stay healthy.  When we are exposed to a bacterial pathogen that causes an infection, we take antibiotics which will kill the pathogen but unfortunately also eradicate the non-harmful bacteria.

How can we specifically target just the bacterial pathogen while leaving the symbiotes of our microbiome intact? Unfortunately, we do not currently have the technology or drugs available that can do this. Research in the McLaughlin lab aims to bridge the gap in knowledge that will allow us to one day make this a reality. 

Our research is centered around the idea that a richer understanding of bacteria as a whole can help us to better target specific strains. We study uncharacterized proteins involved in various processes that are of importance to bacterial systems including antibiotic resistance transfer, carbohydrate utilization, and biosynthetic pathways like fatty acid synthesis.

We use macromolecular x-ray crystallography to investigate protein structure and function. Coupled with molecular biology, biochemical, and biophysical techniques, it allows us to investigate structure-function relationship in various systems.

The three current research projects in the McLaughlin Lab are: (1) spread of antibiotic resistance in Salmonella and Staphylococcus, (2) the commensal human gut bacteria Bacteroides ovatus, and (3) uncharacterized/emerging pathogens proteomes.

An overview of our general experimental strategy for studying target proteins is shown here:

Project #1. Antibiotic resistant bacterial strains pose a major threat to human health.  Conjugative plasmid transfer is a major route for the spread of antibiotic resistant genes, mediated by an essential complex of proteins called the relaxosome.

Resistance genes are contained on extrachromosomal pieces of DNA called conjugative multiresistance plasmids (cMRPs). cMRPs also encode most of the genes for the relaxosome to direct their own cell-to-cell transfer.

This research aims to understand the molecular basis of plasmid propagation and replication may lead to new ways to reduce the prevalence and spread of antibiotic resistance, using cRMPs found in Salmonella typhimurium and Staphylococcus aureus. 

Project #1 Citations (* denotes Vassar College Undergraduate):

  1. Sarosh A, Kwong SM, Jensen SO, Northern F*, Walton WG, Eakes TC, Redinbo MR, Firth N, McLaughlin KJ. pSK41/pGO1-family conjugative plasmids of Staphylococcus aureus encode a cryptic repressor of replication. Plasmid. 2023 Sep-Nov;128:102708. doi: 10.1016/j.plasmid.2023.102708. Epub 2023 Nov 13. PMID: 37967733.

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Project #2. Microbiome dysbiosis, the imbalance of microbial populations in the body, has been implicated in many areas of human health including autoimmune diseases. Gut microbiota populations in healthy individuals show marked differences compared with populations in individuals with autoimmune diseases.

An overabundance of gut microbe Bacteroides ovatus has been observed in the autoimmune disorders systemic lupus erythematosus, Crohn’s disease, type I diabetes, and celiac disease.

This research will provide further understanding of B. ovatus at the molecular level through characterization of  proteins from B. ovatus hypothesized to play a part in provoking a human autoimmune response or on strain survival, that may be of interest for developing new therapies..

  • August 2024: We deposited four new structures of Bacteroides ovatus polysaccharide deacetylase (BoPDA) to the PDB! The paper about BoPDA is currently under review at Biochemistry.

Project #3. In partnership with the National Institute of Allergy and Infectious Diseases (NIAID)’s Seattle Structural Genomics Centers for Infectious Diseases (SSGCID), we are biochemically investigating previously uncharacterized proteins from a range of bacterial human pathogens, starting with Rickettsia felis, Legionella pneumoniae and Mycoliciobacterium smegmatis. A paper investigating a protein from Neisseria gonorrhoeae is also forthcoming. 

The MsFabG4 paper was highlighted on the jornal issue cover (!) and we were intervied as part of a new feature of the Acta Crys F journal called “Interview with the Authors. Watch the interview with my students and I here:

Papers published from project #3

Project #3 Citations (* denotes Vassar College Undergraduate):

  1. Ran X*, Parikh P*, Abendroth J, Arakaki TL, Clifton MC, Edwards TE, Lorimer DD, Mayclin S, Staker BL, Myler P, McLaughlin KJ. Acta Crystallogr F Struct Biol Commun. 2024 Apr 1;80(Pt 4):82-91. doi: 10.1107/S2053230X2400356X. 
  2. Moorefield, J.*, Konuk, Y.*, Norman, J. O.*, Abendroth, J., Edwards, T. E., Lorimer, D. D., Mayclin, S. J., Staker, B. L., Craig, J. K., Barett, K. F., Barrett, L. K., Van Voorhis, W. C., Myler, P. J. & McLaughlin, K. J. (2023). Acta Crystallogr F Struct Biol Commun. F79, 257-266.
  3. Rodarte JV*, Abendroth J, Edwards TE, Lorimer DD, Staker BL, Zhang S, Myler PJ, McLaughlin KJ. Crystal structure of acetoacetyl-CoA reductase from Rickettsia felis. Acta Crystallogr F Struct Biol Commun. 2021 Feb 1;77(Pt 2):54-60.

Bonus- Check out this video with Prof. McLaughlin discussing an introduction to protein structure and a peek into the research in the McLaughlin Lab: