About
Michael R. Sussman is a professor in the Department of Biochemistry at the University of Wisconsin–Madison. His research focuses on cell structure and signaling, quantitative biology, systems and synthetic biology. His laboratory employs advanced proteomic and genomic technologies to investigate complex biological signaling networks, particularly in plants and electric fish. In plant research, his team uses mass spectrometry-based quantitative phosphoproteomics to identify key components of signaling pathways initiated by hormones and osmosensing receptor proteins in Arabidopsis thaliana, aiming to understand receptor-like kinase mediated signaling and posttranslational modifications involved in plant responses to environmental changes such as drought. In addition, his work extends to studying the genetic basis of electrocyte differentiation and function in electric fish, specifically the electric eel Electrophorus electricus, using genomic, transcriptomic, and proteomic technologies. This research seeks to uncover the genes and regulatory networks involved in electrocyte development, with potential applications in medical and energy fields. Furthermore, Sussman's lab collaborates on projects aimed at discovering blood-borne biomarkers for colorectal cancer, utilizing quantitative proteomics to identify and validate serum protein markers for early, minimally invasive detection of the disease. His contributions span fundamental biological research and technological development, advancing understanding in cell signaling, plant biology, neurobiology, and medical diagnostics.
Research topics
- Biology
- Biochemistry
- Botany
- Medicine
- Biophysics
- Genetics
- Biotechnology
- Traditional medicine
- Cell biology
- Chemistry
Selected publications
Plant Proteomics: New Insights Into the Green World Through Advanced Mass Spectrometry
Molecular & Cellular Proteomics · 2025-10-01
editorialOpen accessSenior authorRole of protein and lipid oxidation in hardening of high‐protein bars during storage
Journal of Food Science · 2025-01-01 · 5 citations
articleOpen accessProtein bar hardening negatively impacts shelf life, quality, and consumer acceptance. Although oxidation is known to negatively affect the flavor and texture of foods, the specific roles of lipid and protein oxidation in bar hardening have not been thoroughly investigated. Furthermore, most research has concentrated on dairy proteins, with a notable lack of studies addressing the hardening of plant-based protein bars. We investigated the role of protein and lipid oxidation, Maillard reactions, moisture loss, protein aggregation, and microstructural changes in the hardening of pea, whey, and rice protein bars over a storage period of 6 weeks (hardness increased 7.2×, 5.4×, and 4.4×, respectively). Changes in tryptophan fluorescence, free sulfhydryl content (e.g., loss of 57% for pea and 44% for whey), and carbonyl content demonstrated that pea and whey bars underwent protein oxidation. Lipid oxidation also occurred, demonstrated by increased peroxide and thiobarbituric acid-reactive substance values. Rice bars, however, did not undergo oxidation. Mass spectrometry indicated greater Maillard-reaction-related protein glycations formed in pea and whey bars (6.9% and 7.7%, respectively) than in rice bars (2.1%). SDS-PAGE revealed that pea and whey, but not rice, proteins aggregated during storage. Overall, this study found that moisture loss, protein and lipid oxidation, Maillard reactions, and protein aggregation correlated with bar hardening. Chemical changes may cause protein aggregation, resulting in hardening. Likely because of rice proteins' innate insolubility and disulfide linkages, rice protein bars were less susceptible to chemical changes and aggregation and hardened more slowly than whey and pea protein bars. PRACTICAL APPLICATION: This study shows that lipid and protein oxidation are correlated with protein bar hardening in both pea and whey protein bars. Additionally, this work suggests that rice protein bars may harden more slowly than pea and whey bars. These findings suggest that potential strategies to prevent bar hardening and extend shelf life include (1) adding antioxidants to prevent oxidation and (2) using rice proteins to partially or fully substitute other protein isolates.
Materials Advances · 2025-01-01 · 1 citations
articleOpen accessLaminar wake of single bubble rise in chemical and biological liquids enhances treatment uniformity with cold atmospheric plasma, facilitating precise proteomics for protein-based drug discovery. Generated by Google Gemini.
2025-10-11
peer-reviewNature Communications · 2024-07-16 · 18 citations
articleOpen accessMaintenance of water homeostasis is a fundamental cellular process required by all living organisms. Here, we use the single-celled green alga Chlamydomonas reinhardtii to establish a foundational understanding of osmotic-stress signaling pathways through transcriptomics, phosphoproteomics, and functional genomics approaches. Comparison of pathways identified through these analyses with yeast and Arabidopsis allows us to infer their evolutionary conservation and divergence across these lineages. 76 genes, acting across diverse cellular compartments, were found to be important for osmotic-stress tolerance in Chlamydomonas through their functions in cytoskeletal organization, potassium transport, vesicle trafficking, mitogen-activated protein kinase and chloroplast signaling. We show that homologs for five of these genes have conserved functions in stress tolerance in Arabidopsis and reveal a novel PROFILIN-dependent stage of acclimation affecting the actin cytoskeleton that ensures tissue integrity upon osmotic stress. This study highlights the conservation of the stress response in algae and land plants, and establishes Chlamydomonas as a unicellular plant model system to dissect the osmotic stress signaling pathway.
2024-10-21
peer-reviewSenior authorFEBS Letters · 2024-12-03 · 1 citations
articleOpen accessSenior authorCorrespondingThe plasma membrane proton pump is the primary energy transducing, electrogenic ion pump of the plasma membrane in plants and fungi. Compared to its fungal counterpart, the plant plasma membrane proton pump's regulatory C-terminal domain (CTD) contains an additional regulatory segment that links multiple sensory pathways regulating plant cell length through phosphorylation and recruitment of regulatory 14-3-3 proteins. However, a complete structural model of a plant proton pump is lacking. Here, we performed covalent labeling with mass spectrometric analysis (CL-MS) on the Arabidopsis pump AHA2 to identify potential interactions between the CTD and the catalytic domains. Our results suggest that autoinhibition in the plant enzyme is much more structurally complex than in the fungal enzyme.
American Journal of Botany · 2024-11-17 · 4 citations
articleOpen accessSenior authorPREMISE: A multi-omic approach was used to explore proteins and networks hypothetically important for establishing filament dimorphisms in heterostylous Turnera subulata (Sm.) as an exploratory method to identify genes for future empirical research. METHODS: Mass spectrometry (MS) was used to identify differentially expressed proteins and differentially phosphorylated peptides in the developing filaments between the L- and S-morphs. RNAseq was used to generate a co-expression network of the developing filaments, MS data were mapped to the co-expression network to identify hypothetical relationships between the S-gene responsible for filament dimorphisms and differentially expressed proteins. RESULTS: Mapping all MS identified proteins to a co-expression network of the S-morph's developing filaments identified several clusters containing SPH1 and other differentially expressed or phosphorylated proteins. Co-expression analysis clustered CDKG2, a protein that induces endoreduplication, and SPH1-suggesting a shared biological function. MS analysis suggests that the protein is present and phosphorylated only in the S-morph, and thus active only in the S-morph. A series of CDKG2 regulators, including ATM1, and cell cycle regulators also correlated with the presence of reciprocal herkogamy, supporting our interest in the protein. CONCLUSIONS: This work has built a foundation for future empirical work, specifically supporting the role of CDKG2 and ATM1 in promoting filament elongation in response to SPH1 perception.
Enrichable Protein Footprinting for Structural Proteomics
Journal of the American Society for Mass Spectrometry · 2024-11-20 · 2 citations
articleSenior authorCorrespondingProtein footprinting is a useful method for studying protein higher order structure and conformational changes induced by interactions with various ligands via addition of covalent modifications onto the protein. Compared to other methods that provide single amino acid-level structural resolution, such as cryo-EM, X-ray diffraction, and NMR, mass spectrometry (MS)-based methods can be advantageous as they require lower protein amounts and purity. As with other MS-based proteomic methods, such as post-translational modification analysis, enrichment techniques have proven necessary for both optimal sensitivity and sequence coverage when analyzing highly complex proteomes. Currently used reagents for footprinting via covalent labeling, such as hydroxyl radicals and carbodiimide-based methods, do not yet have a suitable enrichment method, limiting their applicability to whole proteome analysis. Here, we report a method for enrichable covalent labeling built upon the GEE/EDC system commonly used to covalently label aspartic acid and glutamic acid residues. Novel labeling reagents containing alkynyl functionality can be “clicked” to any azido-containing molecule with copper-catalyzed azide–alkyne cycloaddition (CuAAC), allowing for enrichment or further labeling. Multiple azide- and alkyne-containing GEE-like molecules were tested, and the most efficient method was determined to be the EDC-facilitated coupling of glycine propargyl amide (GPA) to proteins. The pipeline we report includes clicking via CuAAC to a commercially available biotin-azide containing a photocleavable linker, followed by enrichment using a streptavidin resin and subsequent cleavage under ultraviolet light. The enrichment process was optimized through the screening of clickable amines, coupling reagents, and enrichment scaffolds and methods with pure model proteins and has also been applied to complex mixtures of proteins isolated from the model plant, Arabidopsis thaliana, suggesting that our method may ultimately be used to measure protein conformation on a proteomic scale.
Radical-Mediated Covalent Azidylation of Hydrophobic Microdomains in Water-Soluble Proteins
ACS Chemical Biology · 2023-07-18 · 3 citations
articleSenior authorCorrespondingHydrophobic microdomains, also known as hydrophobic patches, are essential for many important biological functions of water-soluble proteins. These include ligand or substrate binding, protein–protein interactions, proper folding after translation, and aggregation during denaturation. Unlike transmembrane domains, which are easily recognized from stretches of contiguous hydrophobic sidechains in amino acids via primary protein sequence, these three-dimensional hydrophobic patches cannot be easily predicted. The lack of experimental strategies for directly determining their locations hinders further understanding of their structure and function. Here, we posit that the small triatomic anion N3– (azide) is attracted to these patches and, in the presence of an oxidant, forms a radical that covalently modifies C–H bonds of nearby amino acids. Using two model proteins (BSA and lysozyme) and a cell-free lysate from the model higher plant Arabidopsis thaliana, we find that radical-mediated covalent azidylation occurs within buried catalytic active sites and ligand binding sites and exhibits similar behavior to established hydrophobic probes. The results herein suggest a model in which the azido radical is acting as an “affinity reagent” for nonaqueous three-dimensional protein microenvironments and is consistent with both the nonlocalized electron density of the azide moiety and the known high reactivity of azido radicals widely used in organic chemistry syntheses. We propose that the azido radical is a facile means of identifying hydrophobic microenvironments in soluble proteins and, in addition, provides a simple new method for attaching chemical handles to proteins without the need for genetic manipulation or specialized reagents.
Recent grants
NSF · $1.2M · 2009–2014
NSF · $2.7M · 2016–2022
NSF · $3.2M · 2020–2026
NSF · $1.3M · 2014–2017
NSF · $4.4M · 2007–2012
Frequent coauthors
- 154 shared
Jeffrey F. Harper
University of Nevada, Reno
- 106 shared
Michael Gribskov
Purdue University West Lafayette
- 84 shared
Alice Harmon
University of Florida
- 83 shared
Estelle M. Hrabak
University of New Hampshire
- 83 shared
Catherine W. M. Chan
- 81 shared
Martine Thomas
Université Paris-Sud
- 81 shared
Hugh G. Nimmo
University of Glasgow
- 81 shared
Nigel G. Halford
Rothamsted Research
Education
- 1990
Ph.D., Molecular and Cell Biology
University of California, San Francisco
- 1984
B.S., Molecular and Cell Biology
University of California, Berkeley
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