Nikhil S. Malvankar
Associate Professor of Molecular Biophysics and Biochemistry
Research & Publications
Biography
News
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
- Outer membrane vesicles and the outer membrane protein OmpU govern Vibrio cholerae biofilm matrix assemblyPotapova A, Garvey W, Dahl P, Guo S, Chang Y, Schwechheimer C, Trebino M, Floyd K, Phinney B, Liu J, Malvankar N, Yildiz F. Outer membrane vesicles and the outer membrane protein OmpU govern Vibrio cholerae biofilm matrix assembly. MBio 2024, 15: e03304-23. PMID: 38206049, PMCID: PMC10865864, DOI: 10.1128/mbio.03304-23.
- 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.
- Microbial biofilms as living photoconductors due to ultrafast electron transfer in cytochrome OmcS nanowiresNeu J, Shipps CC, Guberman-Pfeffer MJ, Shen C, Srikanth V, Spies JA, Kirchhofer ND, Yalcin SE, Brudvig GW, Batista VS, Malvankar NS. Microbial biofilms as living photoconductors due to ultrafast electron transfer in cytochrome OmcS nanowires. Nature Communications 2022, 13: 5150. PMID: 36071037, PMCID: PMC9452534, DOI: 10.1038/s41467-022-32659-5.
- A 300-fold conductivity increase in microbial cytochrome nanowires due to temperature-induced restructuring of hydrogen bonding networksDahl PJ, Yi SM, Gu Y, Acharya A, Shipps C, Neu J, O’Brien J, Morzan UN, Chaudhuri S, Guberman-Pfeffer MJ, Vu D, Yalcin SE, Batista VS, Malvankar NS. A 300-fold conductivity increase in microbial cytochrome nanowires due to temperature-induced restructuring of hydrogen bonding networks. Science Advances 2022, 8: eabm7193. PMID: 35544567, PMCID: PMC9094664, DOI: 10.1126/sciadv.abm7193.
- Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalusDuy PQ, Weise SC, Marini C, Li XJ, Liang D, Dahl PJ, Ma S, Spajic A, Dong W, Juusola J, Kiziltug E, Kundishora AJ, Koundal S, Pedram MZ, Torres-Fernández LA, Händler K, De Domenico E, Becker M, Ulas T, Juranek SA, Cuevas E, Hao LT, Jux B, Sousa AMM, Liu F, Kim SK, Li M, Yang Y, Takeo Y, Duque A, Nelson-Williams C, Ha Y, Selvaganesan K, Robert SM, Singh AK, Allington G, Furey CG, Timberlake AT, Reeves BC, Smith H, Dunbar A, DeSpenza T, Goto J, Marlier A, Moreno-De-Luca A, Yu X, Butler WE, Carter BS, Lake EMR, Constable RT, Rakic P, Lin H, Deniz E, Benveniste H, Malvankar NS, Estrada-Veras JI, Walsh CA, Alper SL, Schultze JL, Paeschke K, Doetzlhofer A, Wulczyn FG, Jin SC, Lifton RP, Sestan N, Kolanus W, Kahle KT. Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus. Nature Neuroscience 2022, 25: 458-473. PMID: 35379995, PMCID: PMC9664907, DOI: 10.1038/s41593-022-01043-3.
- Protein nanowires with tunable functionality and programmable self-assembly using sequence-controlled synthesisShapiro DM, Mandava G, Yalcin SE, Arranz-Gibert P, Dahl PJ, Shipps C, Gu Y, Srikanth V, Salazar-Morales AI, O’Brien J, Vanderschuren K, Vu D, Batista VS, Malvankar NS, Isaacs FJ. Protein nanowires with tunable functionality and programmable self-assembly using sequence-controlled synthesis. Nature Communications 2022, 13: 829. PMID: 35149672, PMCID: PMC8837800, DOI: 10.1038/s41467-022-28206-x.
- Making protons tag along with electronsGuberman-Pfeffer MJ, Malvankar NS. Making protons tag along with electrons. Biochemical Journal 2021, 478: 4093-4097. PMID: 34871365, DOI: 10.1042/bcj20210592.
- Structure of Geobacter pili reveals secretory rather than nanowire behaviourGu Y, Srikanth V, Salazar-Morales AI, Jain R, O’Brien J, Yi SM, Soni RK, Samatey FA, Yalcin SE, Malvankar NS. Structure of Geobacter pili reveals secretory rather than nanowire behaviour. Nature 2021, 597: 430-434. PMID: 34471289, PMCID: PMC9127704, DOI: 10.1038/s41586-021-03857-w.
- Roadmap on emerging concepts in the physical biology of bacterial biofilms: from surface sensing to community formationWong GCL, Antani JD, Lele PP, Chen J, Nan B, Kühn MJ, Persat A, Bru JL, Høyland-Kroghsbo NM, Siryaporn A, Conrad JC, Carrara F, Yawata Y, Stocker R, Brun Y, Whitfield GB, Lee CK, de Anda J, Schmidt WC, Golestanian R, O’Toole G, Floyd KA, Yildiz FH, Yang S, Jin F, Toyofuku M, Eberl L, Nomura N, Zacharoff LA, El-Naggar MY, Yalcin SE, Malvankar NS, Rojas-Andrade MD, Hochbaum AI, Yan J, Stone HA, Wingreen NS, Bassler BL, Wu Y, Xu H, Drescher K, Dunkel J. Roadmap on emerging concepts in the physical biology of bacterial biofilms: from surface sensing to community formation. Physical Biology 2021, 18: 10.1088/1478-3975/abdc0e. PMID: 33462162, PMCID: PMC8506656, DOI: 10.1088/1478-3975/abdc0e.
- Intrinsic electronic conductivity of individual atomically resolved amyloid crystals reveals micrometer-long hole hopping via tyrosinesShipps C, Kelly HR, Dahl PJ, Yi SM, Vu D, Boyer D, Glynn C, Sawaya MR, Eisenberg D, Batista VS, Malvankar NS. Intrinsic electronic conductivity of individual atomically resolved amyloid crystals reveals micrometer-long hole hopping via tyrosines. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2014139118. PMID: 33372136, PMCID: PMC7812754, DOI: 10.1073/pnas.2014139118.
- The blind men and the filament: Understanding structures and functions of microbial nanowiresYalcin SE, Malvankar NS. The blind men and the filament: Understanding structures and functions of microbial nanowires. Current Opinion In Chemical Biology 2020, 59: 193-201. PMID: 33070100, PMCID: PMC7736336, DOI: 10.1016/j.cbpa.2020.08.004.
- Electric field stimulates production of highly conductive microbial OmcZ nanowiresYalcin SE, O’Brien J, Gu Y, Reiss K, Yi SM, Jain R, Srikanth V, Dahl PJ, Huynh W, Vu D, Acharya A, Chaudhuri S, Varga T, Batista VS, Malvankar NS. Electric field stimulates production of highly conductive microbial OmcZ nanowires. Nature Chemical Biology 2020, 16: 1136-1142. PMID: 32807967, PMCID: PMC7502555, DOI: 10.1038/s41589-020-0623-9.
- Direct observation of anisotropic growth of water films on minerals driven by defects and surface tensionYalcin SE, Legg BA, Yeşilbaş M, Malvankar NS, Boily JF. Direct observation of anisotropic growth of water films on minerals driven by defects and surface tension. Science Advances 2020, 6: eaaz9708. PMID: 32832658, PMCID: PMC7439304, DOI: 10.1126/sciadv.aaz9708.
- Structure of Microbial Nanowires Reveals Stacked Hemes that Transport Electrons over MicrometersWang F, Gu Y, O’Brien J, Yi SM, Yalcin SE, Srikanth V, Shen C, Vu D, Ing NL, Hochbaum AI, Egelman EH, Malvankar NS. Structure of Microbial Nanowires Reveals Stacked Hemes that Transport Electrons over Micrometers. Cell 2019, 177: 361-369.e10. PMID: 30951668, PMCID: PMC6720112, DOI: 10.1016/j.cell.2019.03.029.
- Expressing the Geobacter metallireducens PilA in Geobacter sulfurreducens Yields Pili with Exceptional ConductivityTan Y, Adhikari RY, Malvankar NS, Ward JE, Woodard TL, Nevin KP, Lovley DR, Beyenal H, Shi L, TerAvest M. Expressing the Geobacter metallireducens PilA in Geobacter sulfurreducens Yields Pili with Exceptional Conductivity. MBio 2017, 8: e02203-16. PMID: 28096491, PMCID: PMC5241403, DOI: 10.1128/mbio.02203-16.
- A Simple and Low‐Cost Procedure for Growing Geobacter sulfurreducens Cell Cultures and Biofilms in Bioelectrochemical SystemsO'Brien JP, Malvankar NS. A Simple and Low‐Cost Procedure for Growing Geobacter sulfurreducens Cell Cultures and Biofilms in Bioelectrochemical Systems. Current Protocols In Microbiology 2016, 43: a.4k.1-a.4k.27. PMID: 27858972, PMCID: PMC5726868, DOI: 10.1002/cpmc.20.
- Reply to 'Measuring conductivity of living Geobacter sulfurreducens biofilms'Malvankar NS, Rotello VM, Tuominen MT, Lovley DR. Reply to 'Measuring conductivity of living Geobacter sulfurreducens biofilms'. Nature Nanotechnology 2016, 11: 913-914. PMID: 27821844, DOI: 10.1038/nnano.2016.191.
- The Low Conductivity of Geobacter uraniireducens Pili Suggests a Diversity of Extracellular Electron Transfer Mechanisms in the Genus GeobacterTan Y, Adhikari RY, Malvankar NS, Ward JE, Nevin KP, Woodard TL, Smith JA, Snoeyenbos-West OL, Franks AE, Tuominen MT, Lovley DR. The Low Conductivity of Geobacter uraniireducens Pili Suggests a Diversity of Extracellular Electron Transfer Mechanisms in the Genus Geobacter. Frontiers In Microbiology 2016, 07: 980. PMID: 27446021, PMCID: PMC4923279, DOI: 10.3389/fmicb.2016.00980.
- Low Energy Atomic Models Suggesting a Pilus Structure that could Account for Electrical Conductivity of Geobacter sulfurreducens PiliXiao K, Malvankar NS, Shu C, Martz E, Lovley DR, Sun X. Low Energy Atomic Models Suggesting a Pilus Structure that could Account for Electrical Conductivity of Geobacter sulfurreducens Pili. Scientific Reports 2016, 6: 23385. PMID: 27001169, PMCID: PMC4802205, DOI: 10.1038/srep23385.
- 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.
- Functional environmental proteomics: elucidating the role of a c-type cytochrome abundant during uranium bioremediationYun J, Malvankar NS, Ueki T, Lovley DR. Functional environmental proteomics: elucidating the role of a c-type cytochrome abundant during uranium bioremediation. The ISME Journal: Multidisciplinary Journal Of Microbial Ecology 2015, 10: 310-320. PMID: 26140532, PMCID: PMC4737924, DOI: 10.1038/ismej.2015.113.
- Impedance Spectroscopy of Ionic Ligand‐Modulated Charge Transport of Gold Nanoparticle FilmsYu X, Malvankar N, Landis R, Eymur S, Miranda OR, Rotello VM. Impedance Spectroscopy of Ionic Ligand‐Modulated Charge Transport of Gold Nanoparticle Films. Small 2015, 11: 3814-3821. PMID: 25919594, DOI: 10.1002/smll.201500127.
- 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.