Melissa Goellner Mitchum was born in New Jersey and spent her formative years in the Yakima Valley of Washington State. She earned a B.S. degree in biology from the University of Puget Sound in 1993, an M.S. degree in plant pathology from the University of Nebraska in 1995, and a Ph.D. degree in plant pathology from North Carolina State University in 2001. She then spent 2 years investigating plant gibberellin biosynthesis and signaling as a post-doctoral associate at Duke University before being hired as an assistant professor at the University of Missouri in 2003 to develop a program in plant nematology. The success of her nematology program at the University of Missouri not only earned her promotion to associate professor in 2010, it has solidified her reputation as a recognized leader in molecular plant nematology at national and international levels. She has made multiple significant discoveries that have resulted in seminal publications within the discipline of plant nematology—they represent exceptional professional achievements for an individual at this stage of her career.
Mitchum was a key investigator in a 2005 Molecular Plant Pathology research report that presented the remarkable discovery of expressed soybean cyst nematode (SCN), Heterodera glycines, effector proteins that were molecular and functional mimics of endogenous plant CLAVATA3/ESR (CLE) peptides—the first time CLE signaling peptides had been identified outside of the plant kingdom. A 2010 New Phytologist paper from her lab presented a comprehensive analysis of HgCLE function and discovered two primary HgCLE types. The two types differed in variable domain amino acid sequences upstream of the active CLE peptide motif that were related to function in different host plant species. Antibody probes that were raised to HgCLE localized the secreted cyst nematode CLE peptide within the cytoplasm of host root feeding cells (syncytia)—a first visual confirmation of the secretion of phytonematode effectors directly into host plant cells that supported decades of related evidence. Through an extensive series of domain swapping experiments, Mitchum’s lab was able to demonstrate that the HgCLE variable domain was critical for proper processing of the active CLE peptide and for trafficking the CLE peptide to extracellular peptide receptors on the host cell plasmalemma. Complementary studies in Mitchum’s lab published in MPMI, The Plant Journal, and Plant Biotechnology Journal have demonstrated that endogenous receptors for native plant CLE signaling peptides, such as CLAVATA1/2, CORYNE, and a RECEPTOR-LIKE PROTEIN KINASE, are also active in the function of the HgCLE effector in plants.
Research on another SCN effector protein in Mitchum’s lab, a novel effector protein called Hg19C07, demonstrated once again that nematodes can recruit endogenous plant processes to promote a parasitic interaction. A 2011 Plant Physiology paper from her lab demonstrated the direct interaction of the Heterodera schachtii ortholog of Hg19C07 (Hs19C07) with a plant LAX3 auxin influx protein at target sites on the plant cell plasmalemma. A related local increase in LAX3 expression was identified within developing syncytia that extended to adjacent cells to be incorporated into the growing syncytium. Expression of Hs19C07 in Arabidopsis thaliana accelerated lateral root formation—a phenotype consistent with altered auxin accumulation in plant cells. This was the first demonstration of potential direct augmentation of localized plant hormone accumulation by a secreted nematode effector protein and confirmed reported observations that altered auxin influx and efflux were active in nematode feeding site formation.
Not only has Mitchum made important discoveries in nematode effector protein function, but as intimated above, she maintains a significant presence in research on the plant side of the parasitic interaction. In an elegant set of experiments reported in MPMI in 2007, her lab conducted the first investigations of gene expression in syncytial cells formed by SCN using laser capture microdissection (LCM) coupled with high-density plant microarray analyses. The sensitivity of the LCM assay identified 1,680 additional plant genes that were differentially expressed within syncytial cells compared with only 85 expressed plant genes in common found using excised root infection sites. The timing of these changes in plant gene expression was identified at 2 days postinfection (dpi) by nematodes—providing some of the earliest known molecular plant response to nematode infection that currently exists. Expression of coordinated groups of plant genes were demonstrated to be up- and down-regulated in syncytia among 2, 5, and 10 dpi and included processes related to plant cell metabolism, cell wall architecture, signaling and transport, and plant defense responses. A more recent plant gene expression profiling study from Mitchum’s lab published in a 2011 Plant Physiology report included the first differential analyses of near-isogenic soybean lines (NILs) differing in the rhg1-b gene that confers resistance to SCN from soybean plant introduction (PI) 88788. Genes encoding an amino acid transporter and SNAP protein were among the plant genes identified to be upregulated during SCN infection of the resistant soybean NIL. These genes were subsequently identified in 2012 by other researchers as part of a cluster of three genes that constitute the rhg1 SCN resistance locus in soybean.
The first source of SCN resistance incorporated into cultivated soybean was from PI 548402 (Peking) and is conditioned by both the Rhg1 and Rhg4 major genes. Mitchum’s lab recently collaborated with scientists analyzing soybean NILs and TILLING mutants at Southern Illinois University to confirm the identity of Rhg4 as a serine hydroxymethyltransferase (SHMT) in a research report published in Nature in October 2012. The SHMT enzyme is conserved across kingdoms and plays a central role in cellular one-carbon and folic acid metabolism. Through a new application of VIGS for nematode infection of soybean roots and a series of complementation assays led by Mitchum’s lab, the PI 548402 allele of Rhg4 (SHMT) was confirmed to confer soybean resistance to SCN. The identification of SHMT as a disease resistance gene was a first of its kind and represented a paradigm shift in our current thinking of the genetic basis of disease resistance to pathogens.