Nikhil S. Malvankar
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Research Summary
How do bacteria breathe without oxygen or soluble electron acceptors? Structures, functions and electron transfer mechanisms of proteins nanowires.
Deep in the ocean or underground, where there is no oxygen, diverse microbes “breathe” by projecting tiny protein filaments called "nanowires" into the soil, to dispose of excess electrons resulting from the conversion of nutrients to energy. These nanowires enable the bacteria to perform environmentally important functions such as cleaning up radioactive sites, generating electricity or sharing electrons with other bacteria. Although it has been known that Geobacter make nanowires, it was not clear what they are actually made of and why they are conductive.
Recent discoveries by our lab resolve two decades of confounding observations in thousands of publications that thought these nanowires as pili filaments (Current Opinion 2020). Our studies have revealed a surprise: the protein nanowires have a core of metal-containing molecules called hemes .By “sequencing” with cryo-electron microscopy, we found that hemes line up to create a continuous path along which electrons travel. Using multimodal functional imaging (Physical Biology 2020) and a suite of electrical, biochemical and physiological studies, we find that rather than pili, nanowires are composed of cytochromes OmcS and OmcZ that transport electrons via seamless stacking of hemes over micrometers (Cell 2019, Nature Chem.Bio. 2020, Nature 2021).
Extensive Research Description
Three major research themes of our lab:
1) Mechanism of ultrafast electron transport & storage:We are determining how nanowires move electrons, ions, spins and excitons at ultrafast (~ 100 fs) rates and centimeter distances unprecedented in biology. We have found a novel electron escape route in proteins to avoid oxidative damage (PNAS 2021) and how cooling speeds up electrons (Science Adv. 2022).
2) Architecture of nanowire electron transport system. We are identifying the nanowire biogenesis and secretion machinery using genetic tools combined with cryo-electron microscopy and tomography and reconstituting the machinery into new species (Nature Comm. 2022).
3) Reducing global temperatures by capturing atmospheric methane produced by microbial consortia. How to lower rising global temperatures by capturing methane released to the atmosphere by microbes? We are lowering the nanowire-mediated respiration rate of methane-producing microbes that are producing more CO2 than that can be used by plants.
Projects involve structural studies, genetically engineering nanowires using synthetic biology tools, nanoscale electron transfer measurements in nanowires and living biofilms, multimodal imaging and spectroscopy, electrochemistry as well as building and experimentally testing computational models (with Victor Batista and Gary Brudvig, Yale Chemistry).
We have several interdisciplinary projects embedded in these larger goals that would be great rotation projects as they provide training in a variety of biophysical, molecular biology and biochemical techniques and are likely to yield positive results/publications within the rotation. Please chat to match your interests with training opportunities. Projects are experimentally or computationally oriented with possibilities of combining both. No prior background is necessary.
Coauthors
Research Interests
Bacteria, Anaerobic; Bacterial Adhesion; Bacterial Infections; Biophysics; Chemistry, Physical; Electron Transport; Environmental Microbiology; Microscopy, Atomic Force; Nanotechnology
Public Health Interests
Environmental Health; Infectious Diseases; Respiratory Disease/Infections
Research Images
Selected Publications
- 195 Aberrant Brain Biomechanics Initiates Ventricular Dilation in a Genetic Subtype of Congenital HydrocephalusPhan D, Dahl P, Koundal S, Pedram M, Deniz E, Benveniste H, Malvankar N, Kahle K. 195 Aberrant Brain Biomechanics Initiates Ventricular Dilation in a Genetic Subtype of Congenital Hydrocephalus Neurosurgery 2023, 69: 32-32. DOI: 10.1227/neu.0000000000002375_195.
- Author Correction: Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunctionXing H, Huang Y, Kunkemoeller B, Dahl P, Muraleetharan O, Malvankar N, Murrell M, Kyriakides T. Author Correction: Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction Scientific Reports 2023, 13: 4253. PMID: 36918662, PMCID: PMC10015071, DOI: 10.1038/s41598-023-31191-w.
- Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivityGu Y, Guberman-Pfeffer M, Srikanth V, Shen C, Giska F, Gupta K, Londer Y, Samatey F, Batista V, Malvankar N. Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivity Nature Microbiology 2023, 8: 284-298. PMID: 36732469, PMCID: PMC9999484, DOI: 10.1038/s41564-022-01315-5.
- Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunctionXing H, Huang Y, Kunkemoeller B, Dahl P, Muraleetharan O, Malvankar N, Murrell M, Kyriakides T. Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction Scientific Reports 2022, 12: 22474. PMID: 36577792, PMCID: PMC9797577, DOI: 10.1038/s41598-022-26337-1.
- Conductivity of individual Geobacter piliAdhikari R, Malvankar N, Tuominen M, Lovley D. Conductivity of individual Geobacter pili RSC Advances 2016, 6: 8354-8357. DOI: 10.1039/c5ra28092c.
- Electronic Conductivity in Living Biofilms: Physical Meaning, Mechanisms, and Measurement MethodsMalvankar N, Lovley D. Electronic Conductivity in Living Biofilms: Physical Meaning, Mechanisms, and Measurement Methods 2015, 211-248. DOI: 10.1002/9781119097426.ch7.
- Aromatic Amino Acids Required for Pili Conductivity and Long-Range Extracellular Electron Transport in Geobacter sulfurreducensVargas M, Malvankar N, Tremblay P, Leang C, Smith J, Patel P, Snoeyenbos-West O, Nevin K, Lovley D. Aromatic Amino Acids Required for Pili Conductivity and Long-Range Extracellular Electron Transport in Geobacter sulfurreducens MBio 2013, 4: e00210-13. PMCID: PMC3622933, DOI: 10.1128/mbio.00210-13.
- Engineering Geobacter sulfurreducens to produce a highly cohesive conductive matrix with enhanced capacity for current productionLeang C, Malvankar N, Franks A, Nevin K, Lovley D. Engineering Geobacter sulfurreducens to produce a highly cohesive conductive matrix with enhanced capacity for current production Energy & Environmental Science 2013, 6: 1901-1908. DOI: 10.1039/c3ee40441b.
- Cover Picture: Supercapacitors Based on c‐Type Cytochromes Using Conductive Nanostructured Networks of Living Bacteria (ChemPhysChem 2/2012)Malvankar N, Mester T, Tuominen M, Lovley D. Cover Picture: Supercapacitors Based on c‐Type Cytochromes Using Conductive Nanostructured Networks of Living Bacteria (ChemPhysChem 2/2012) ChemPhysChem 2012, 13: 365-365. DOI: 10.1002/cphc.201290005.
- Promoting direct interspecies electron transfer with activated carbonLiu F, Rotaru A, Shrestha P, Malvankar N, Nevin K, Lovley D. Promoting direct interspecies electron transfer with activated carbon Energy & Environmental Science 2012, 5: 8982-8989. DOI: 10.1039/c2ee22459c.
- Comment on “On electrical conductivity of microbial nanowires and biofilms” by S. M. Strycharz-Glaven, R. M. Snider, A. Guiseppi-Elie and L. M. Tender, Energy Environ. Sci. , 2011, 4 , 4366Malvankar N, Tuominen M, Lovley D. Comment on “On electrical conductivity of microbial nanowires and biofilms” by S. M. Strycharz-Glaven, R. M. Snider, A. Guiseppi-Elie and L. M. Tender, Energy Environ. Sci. , 2011, 4 , 4366 Energy & Environmental Science 2012, 5: 6247-6249. DOI: 10.1039/c2ee02613a.
- Biofilm conductivity is a decisive variable for high-current-density Geobacter sulfurreducens microbial fuel cellsMalvankar N, Tuominen M, Lovley D. Biofilm conductivity is a decisive variable for high-current-density Geobacter sulfurreducens microbial fuel cells Energy & Environmental Science 2012, 5: 5790-5797. DOI: 10.1039/c2ee03388g.
- Lack of cytochrome involvement in long-range electron transport through conductive biofilms and nanowires of Geobacter sulfurreducensMalvankar N, Tuominen M, Lovley D. Lack of cytochrome involvement in long-range electron transport through conductive biofilms and nanowires of Geobacter sulfurreducens Energy & Environmental Science 2012, 5: 8651-8659. DOI: 10.1039/c2ee22330a.
- Bacterial biofilms: the powerhouse of a microbial fuel cellFranks A, Malvankar N, Nevin K. Bacterial biofilms: the powerhouse of a microbial fuel cell Biofuels 2010, 1: 589-604. DOI: 10.4155/bfs.10.25.