Dr. Thomas Merritt

Genomics and Bioinformatics - Canada Research Chair

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Research Involves

Using genomics and bioinformatics to investigate the connection between genotypes and phenotypes.

 

Research Relevance

This research will lead to a better understanding of molecular complexity and protein function.

 

Connecting the Dots between Genes and Traits

Genetics permeates our modern culture. From grade school, students now understand the fundamentals of molecular genetics—that physical characters, from the colour of our eyes to the shape of a pea, are determined by packets of information we call “genes.” Many even know that genes are made up of DNA, that differences between gene copies—“alleles”—make up an organism’s “genotype”, and that the characteristics they lead to are called “phenotypes.”

Surprisingly, though, we still do not really understand how genotypes and phenotypes are connected. Several different projects in the laboratory of Dr. Thomas Merritt, Canada Research Chair in Genomics and Bioinformatics, are investigating this connection by looking at different organisms, from microbes to fruit flies to fish.

Merritt’s research explores biological diversity and its underlying genetic architecture by combining bioinformatics—the computer-based examination of gene, genotype and genome (all the genes in an organism)—with functional genomics, or direct manipulation and experimentation.

In one project, student researchers are using genetically engineered fruit flies to investigate how their metabolism affects things such as how long they live and how much fat they store. In another project, Merritt’s team is looking at the genome of an entire community of microbes able to thrive in contaminated mine waste, in the hopes of understanding the community’s metabolic potential.

Knowing that genetic interactions are complex and sometimes counterintuitive, Merritt’s team is developing a better understanding of molecular complexity and protein function in order to tackle a wide range of challenges, from metabolic disease to biological stress to industrial waste clean-up.

 

Click here for TEDx's video Genetics - Why most of what Im going to tell you is wrong
Click here for TVO's video Big Ideas: Thomas Merritt on genetics, talents and aptitudes

BIOL-4807EL - Advanced Genetics

CHMI-4206EL - Applied Bioinformatics

CHMI-3227EL - Experimental Biochemistry

CHMI-5266EL - Molecular Evolution

Graduate Student Positions: Functional Genomics and Metabolomics

Merritt Lab, Department of Chemistry & Biochemistry, Laurentian University

Graduate positions to study a variety of systems linked by common questions investigating the connection between genotype and phenotype are available in the Merritt Lab. Both MSc and PhD positions are available to start May-September 2013.

Current areas of investigation focus on network function, metabolomic complexity, and gene expression in flies and microbes. Successful applicants will be expected to develop research projects of their own that complement and build on these areas.                                                                  

 

NETWORK METABOLOMICS

Much of my research program investigates interactions across simple metabolic networks as models of biological complexity. Often using Drosophila melanogaster, this research combines naturally occurring and laboratory engineered genetic variation with biochemical, physiological, and complex biological phenotypes to quantify the connection between genetic variation and biological complexity. Working with D. melanogaster allows us to combine cutting edge molecular genetics with natural population genetic diversity to investigate the function and evolution of network complexity. This work is expanding our understanding of interactions within networks and the importance of the overall genetic background. Our results have implications both in the application of model systems and in the importance of inter-individual genetic variation. Current directions in this research include expanding the search for network metabolites using broad-based liquid chromatography / mass spectrometry (LC/MS).

 

MICROBIAL DIVERSITY AND METABOLOMIC COMPLEXITY

My lab is also using LC/MS for metabolomic profiling to quantify interactions within microbial communities. This research will use naturally occurring and lab cultured communities with increasing species richness to quantify interactions within these communities with a focus on the distinct microbial communities of Acid Mine Drainage (AMD) environments. AMD, highly acidic water draining from mine waste, is a global environmental issue that largely results from microbial metabolism of mining contaminates. As such, the microbial communities are of great environmental and economic interest. These communities are also strikingly simple, facilitating their study and reconstruction, making them an exciting system for understanding the fundamental science of community interactions and metabolomics. This research combines the publicly available genomic and metagenomic libraries for many of the dominant AMD microbes with developing LC/MS-based metabolomic profiling to establish the connections between species and genome diversity and metabolic complexity. This work will be co-supervised with Drs. Nadia Mykytczuk and Leo Leduc in the Department of Biology at Laurentian University.

 

INFLUENCE OF GENOMIC ARCHITECTURE AND DIVERSITY ON GENE EXPRESSION

Conventional models of gene regulation focus on cis-regulation, the control of transcription by regulatory elements on the chromosome being transcribed. Recent research has highlighted the importance of trans-regulation, the influence of one chromosome on the expression of the other, essentially crosstalk between chromosomes and a form of epigenetic regulation. Trans-regulation is much more poorly understood than cis-, but is a fast developing field with implications in both “normal” and disease state gene expression; trans-regulation appears to be the norm in flies, but has been implicated in disregulation of gene expression in some human cancers. My lab has been developing a model system in D. melanogaster that is extremely sensitive and experimentally tractable. Current research is investigating the role of both local and global factors in driving these trans-interactions.

The Merritt Lab is funded by grants from the Canadian Foundation for Innovation (CFI) and the Natural Sciences and Engineering Research Council (NSERC), including a Tier 2 Canada Research Chair. Laurentian University is a bilingual institution offering courses in both French and English. Laurentian University is a bilingual institution offering courses in both French and English.

Applicants should be independently motivated, have a good academic record, and have demonstrated both an interest in and aptitude for research. Please send an application with unofficial transcripts, a brief CV including contact information for two references, to:

 

tmerritt@laurentian.ca 

Tier 2 Canada Research Chair in Genomics and Bioinformatics

Associate Professor

Department of Chemistry & Biochemistry

Laurentian University

935 Ramsey Lake Road

Sudbury, ON, P3E 2C6, Canada.

Assistant Professor

Tier II Canada Research Chair in Genomics and Bioinformatics

Department of Chemistry and Biochemistry

Office: Fraser 310

tmerritt@laurentian.ca  

 

Laurentian University

935 Ramsey Lake Rd

Sudbury, Ontario P3E 2C6

705-675-1151 ext. 2189

 

Thomas Lum

MSc Student

Department of Chemistry & Biochemistry

Office: Fraser 315a

tx_lum@laurentian.ca

 

Teresa Rzezniczak

MSc Student

Department of Chemistry & Biochemistry

Office: Fraser 315a

tz_rzezniczak@laurentian.ca

 

Robert Harniman

MSc Student

Department Biology

Office: Fraser 315a

rx_harniman@laurentian.ca

 

Kristine Bernard

MSc Student

Department of Biology

Office: Fraser 315a

ke_bernard@laurentian.ca

 

Laura Douglas

Undergraduate Thesis Student

Department of Chemistry & Biochemistry

Office: Fraser 315a

la_douglas@laurentian.ca

 

Ryan Dugas

Undergraduate Thesis Student

Department of Chemistry & Biochemistry

Office: Fraser 315a

rx_dugas@laurentian.ca

Bing, X, TZ Rzezniczak, JR Bateman, TJS Merritt 2014 Transvection-Based Gene Regulation in Drosophila Is a Complex and Plastic Trait. G3 4(11): 2175-2187. pdf
  

Knee, JM, TZ Rzezniczak, K Guo, A Barsh, TJS Merritt 2013 A novel ion pairing LC-MS metabolomics protocol for study of a variety of biologically relevant metabolites. Journal of Chromatography B 936: 63-73. pdf

 

Harniman, R, TJS Merritt, LJ Chapman, D. Lesbarreres, ML Martinez 2013 Population differentiation of the African cyprinid Barbus neumayeri across dissolved oxygen regimes. Ecology and Evolution 3(6): 1495-1506. pdf

 

Auld, R, M Myre, NCS Mykytczuk, LG Leduc, TJS Merritt 2013 Characterization of the microbial acid mine drainage microbial community using culturing and direct sequencing techniques. Journal of Microbial Methods 93: 108-115. 

 pdf

 

Auld, R, JM Quattro, TJS Merritt 2012 Molecular evolution of teleost neural isozymes. Journal of Molecular Evolution 75:198-213. 

 pdf

 

Rzezniczak, TZ, TE Lum, R Harniman, TJS Merritt 2012 A combination of structural and cis-regulatory factors drive biochemical differences in Drosophila melanogaster malic enzyme. Biochemical Genetics 50: 823-837. pdf

 

Rzezniczak, TZ and TJS Merritt 2012 Interactions of NADP-reducing enzymes across varying environmental conditions: a model of biological complexity. G3 Gene, Genomes, Genetics 2: 1613-1623. pdf

 

Paula, MT, AP Zemolin, AP Vargas, RM Golombieski, ELS Loreto, AP Saidelles, RS Picoloto, EMM. Flores, AB Pereira, JBT Rocha, TJS Merritt, JL Franco, and T Posser 2012 Effects of Hg(II) Exposure on MAPK Phosphorylation and Antioxidant System in D. melanogaster. Environmental Toxicology DOI: 10.1002/tox.21788. pdf

 

Babin-Fenske, JJ, TJS Merritt, JM Gunn, T Walsh, and D Lesbarreres 2012 Phylogenetic analysis of Hyalella colonization in lakes recovering from acidification and metal contamination. Canadian Journal of Zoology 90:624-629. pdf

 

Lum, T.E. and T.J.S. Merritt 2011 Non-classical Regulation of Transcription: Interchromosomal-interactions at the Malic Enzyme Locus of Drosophila melanogaster Genetics 189: 837-849. pdf

 

Rzezniczak, T.Z., L. Douglas, J.H. Watterson, and T.J.S. Merritt 2011 Paraquat administration in Drosophila for use in metabolic studies of oxidative stress. Analytical Biochemistry 419:345-347.pdf

 

Bernard, K.E., T.L. Parkes, and T.J.S. Merritt 2011 A Model of Oxidative Stress Management: Moderation of Carbohydrate Metabolizing Enzymes in SOD1-Null Drosophila melanogaster. PLoS ONE. 6:e24518. pdf

 

Merritt, T.J.S., Douglas, L. Rzeznickzak, and J.H. Watterson. 2011 Rapid and Simple Analysis of Paraquat in Tissue Homogenate by Ultra-High Performance Liquid Chromatography. Analytical Methods 419:345-347. pdf

 

Yang, C-S, M.J. Thomenius, E. C. Gan, W. Tang, C. D. Freel, T.J.S. Merritt, L. K. Nutt, and S. Kornbluth. 2010 Metabolic regulation of Drosophila apoptosis through inhibitory phosphorylation of Dronc. The EMBO Journal 29: 2715-2723. pdf

 

Merritt, T.J.S, Kuczynski, K, E. Sezgin, C-T Zhu, S. Kumagai and W. F. Eanes. 2009 Quantifying Interactions within the NADP(H) Network in Drosophila melanogaster. Genetics 182: 564-574.  pdf

 

Eanes, W. F., T. J. S. Merritt, J. M. Flowers, S. Kumagai, C.-T. Zhu.  2009 Direct evidence that genetic variation in glycerol-3-phosphate and malate dehydrogenase genes (Gpdh and Mdh1) affects adult ethanol tolerance in Drosophila melanogaster. Genetics 181: 607-614. pdf

 

Eanes, W. F., T. J. S. Merritt, J. M. Flowers, S. Kumagai, E. Sezgin, C.-T. Zhu.  2006 Flux Control and excess capacity in the enzymes of glycolysis and their relationship to flight metabolism in Drosophila melanogaster. Proc. Nat. Acad. Sci. USA 103: 19413-19418. pdf

 

Merritt, T. J. S., E. Sezgin, C. T. Zhu, and W. F. Eanes. 2006 Triglyceride pools, flight, and genetic variation at the Gpdh locus in Drosophila melanogaster.  Genetics 172: 293-304. pdf

 

Merritt, T. J. S., D. D. Duvernell, and W. F. Eanes. 2005 Natural and synthetic alleles provide complementary insights into the nature of selection acting on the Men polymorphism of Drosophila melanogaster.  Genetics 171: 1707-1718. pdf

 

Merritt, T. J. S., C. R. Young, R. G. Vogt, R. C. Wilkerson, and J. M. Quattro. 2005. Intron retention identifies a malarial vector within the Anopheles (Nyssorhynchus) albitaris complex (Diptera: Culicidae).  Molecular Phylogeneitcs and Evolution 35(3): 719-724. pdf

 

Matzkin†, L. M., T .J. S. Merritt†, C. T. Zhu, and W. F. Eanes. 2005. The structure and population genetics of the breakpoints associated with cosmopolitan inversion In(3R)Payne in Drosophila melanogaster.  Genetics 170: 1143-1152.  † This is a jointly first authored paper with Dr. Matzkin.pdf

 

Merritt, T. J. S. and J. M. Quattro. 2003. Evolution of the vertebrate cytosolic malate dehydrogenase gene family: Duplication and divergence in actinopterygian fish. Journal of Molecular Evolution 56(3): 265-276. pdf

 

Merritt, T. J. S. and J. M. Quattro. 2002. Negative charge correlates with neural expression in vertebrate aldolase isozymes. Journal of Molecular Evolution 55(6): 674-683. pdf

 

Merritt, T. J. S. and J. M. Quattro. 2001. Evidence for a period of directional selection following gene duplication in a neurally-expressed locus of triosephosphate isomerase. Genetics 159(2): 689-697. pdf

 

Merritt, T. J. S., L. Shi, M. C. Chase, M. A. Rex, R. J. Etter, and J. M. Quattro. 1998. "Universal" cytochrome b primers facilitate intraspecific comparisons in Molluscan taxa. Molecular Marine Biology and Biotechnology 7: 7-11. pdf

 

Merritt, T. J. S., S. LaForest, G. D. Prestwich, J. M. Quattro, and R. G. Vogt. 1998. Patterns of gene duplication in Lepidopteran pheromone binding proteins. Journal of Molecular Evolution 46: 272-276. pdf

 

Knee, JM, TZ Rzezniczak, K Guo, A Barsh, TJS Merritt 2013 A novel ion pairing LC-MS metabolomics protocol for study of a variety of biologically relevant metabolites. Journal of Chromatography B 936: 63-73. pdf

My research investigates the evolution and control of genes and genetic networks.  Genes evolve through time, but proteins, not genes, are under selection.  A central challenge in my research is determination of rules that govern the connection between genotypes and phenotypes.

 

EVOLUTION AND REGULATION OF A SIMPLE METABOLIC NETWORK

A set of research projects in my lab use the NADP-reducing metabolic enzymes in Drosophila melanogaster (the fruit fly) as a model system for metabolic control and the evolution of genetic networks.  These enzymes, Men, Idh, G6pd and 6pgd, connected by a shared metabolic cofactor (NADP), form a discrete network small enough to be experimentally manageable, yet large enough to include complex and interesting interactions.  We have found that the enzymatic activity of any one member of the network is dependent on the activities of the other members, suggesting complex interactions between alleles.  Recent studies are including double mutants and expanding into effector molecules, such as Superoxide Dismutase, that use NADPH to reduce oxidized molecules.

 

EVOLUTION AND REGULATION OF A SIMPLE METABOLIC NETWORK: STRESS

Model systems, such as drosophila, are invaluable tools in explaining the basic genetics and biochemistry of other, less easily manipulated, species.  An often unaddressed question, however, is the consistency in interactions between species and conditions.  In addition to quantifying the interactions among members of the NADP(H) network under benign conditions, my lab is quantifying these same interactions in flies under oxidative stress.   Oxidative stress was chosen because of the role of NADPH in combatting this stressor.

 

TRANSVECTION: INTER-ALLELIC GENE REGULATION

Regulatory elements on homologous chromosomes have been shown to interact to regulate gene expression in a number of species and loci.  My lab studies this regulation using engineered alleles for various metabolic enzymes following both protein activity and gene expression.  This study promises to further understanding of gene regulation, the genomic architecture of regulatory regions as well as the an interesting twist in the genotype-phenotype connection.