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Home » Archives for December 2023

December 2023

Archives for December 2023

Faculty Publications – 2023

December 1, 2023 by ljudy@utk.edu

  1. Acharyya D, Cooper J and Prosser RA. Ex vivo comparative investigation of suprachiasmatic nucleus excitotoxic resiliency F1000Research 2023, 11:1242.
  2. Adhikari A, Khanal S, Magar SR, Thapa S, Khati S, Lamichhane R, Marasini K. (2023) Aspergillus Coinfection in a Hydatid Cyst Cavity of Lung in an Immunocompetent Host: A Case Report and Review of Literature Case Reports in Infectious Diseases https://doi.org/10.1155/2023/6975041.
  3. Adhikari A, Shrestha S, Bhattarai P, Khanal S, Lamichhane R, Balayar R, Panta S, Marasini K. (2022) Cleidocranial dysplasia—A case report of incidentally found and lately diagnosed disorder Clinical Case Reports 10 (10), e6440.
  4. Agarwal R and Smith JC. Speed vs accuracy: Effect on ligand pose accuracy of varying box size and exhaustiveness in AutoDock Vina Molecular Informatics 42(3) 2200188 (2023). 
  5. Ancajas CJ, Alam A, Alves DS, Zhou Y, Wadsworth NM, Cassilly CD, Ricks TJ, Carr AJ, Reynolds TB, Barrera BN, Best MD. (2023) Cellular Labeling of Phosphatidylserine Using Clickable Serine Probes. ACS Chemical Biology 18 (2), 377-384.
  6. Azhar BJ, Abbas S, Aman S, Yamburenko MV, Chen W, Müller L, Jewell DA, Dong J, Shakeel SN, Groth G, Binder BM, Grigoryan G, Schaller GE. (2023) Basis for high-affinity ethylene binding by the ethylene receptor ETR1 of Arabidopsis. Proceedings of the National Academy of Sciences, USA. 120: e2215195120.
  7. Bogati B, Wadsworth N, Barrera F, Fozo EM. Improved growth of Escherichia coli in aminoglycoside antibiotics by the zor-orz toxin-antitoxin system. Journal of Bacteriology (2022) JB0040721. doi: 10.1128/JB.00407-21 PMID: 34570627.
  8. Brenya E, Dutta E, Herron B, Walden LH, Roberts DM, and Binder BM. (2023) Ethylene-Mediated Metabolic Priming Increases Photosynthesis and Metabolism to Enhance Plant Growth and Stress Tolerance. PNAS-Nexus doi: 10.1093/pnasnexus/pgad216.
  9. Brueggeman JM, Windham IA, Nebenführ A (2022) Nuclear movement in growing Arabidopsis root hairs involves both actin filaments and microtubules. Journal of Experimental Botany 73: 5388-5399. DOI: 10.1093/jxb/erac207. PMID: 35554524.
  10. Das P, San Martin R, McCord RP. Differential contributions of nuclear lamina association and genome compartmentalization to gene regulation. Nucleus. 2023 Dec;14(1):2197693. doi: 10.1080/19491034.2023.2197693. PubMed PMID: 37017584; PubMed Central PMCID: PMC10078145.
  11. Dockendorff TC, Estrem B, Reed J, Simmons JR, Bahrami Zadegan S, Zagoskin MV, Terta V, Seaberry E, Wang J: The Nematode Oscheius tipulae as A Genetic Model for Programmed DNA Elimination. Current Biology. 2022, 32(23):5083-5098. https://doi.org/10.1016/j.cub.2022.10.043.
  12. Espinoza-Araya, C., Starbird, R., Prasad, E.S., Venkatesan, R., Mulchandani, A., Bruce, B.D, and Villarreal, C.C., (2023) A bacteriorhodopsin-based biohybrid solar cell using carbon-based electrolyte and cathode components. BBA-Bioenergetics, 1864:4, 148985; https://doi.org/10.1016/j.bbabio.2023.148985.
  13. Estrem B, Wang J: Programmed DNA elimination in the parasitic nematode Ascaris. PLoS Pathogens. 2023 Feb; 19(2):e1011087. https://doi.org/10.1371/journal.ppat.1011087.
  14. Ganusova, E.E., Rost, M., Aksenova, A., Abdulhussein, M., Holden, A. and Alexandre, G. 2023. Azospirillum brasilense AerC and Tlp4b Cytoplasmic Chemoreceptors are promiscuous and interact with the two Membrane-Bound Chemotaxis Signaling Clusters mediating chemotaxis responses. J Bacteriol 205(6): e0048422.; doi: 10.1128/jb.00484-22.
  15. Gao, J., Carnahan, J., Alexandre, G. and Trolinger J. 2022. “Digital holographic microscopy for volumetric, three-dimensional characterization of bacterial motility,” Proc. SPIE 12223, Interferometry XXI, 122230E (3 October 2022); https://doi.org/10.1117/12.2633136.
  16. Gray ALH, Norman V, Oluwatoba DS, Prosser RA, Do TD. Potential Protective Function of Aβ42 Monomer on Tauopathies. J Am Soc Mass Spectrom. 2023 Mar 1;34(3):472-483. 
  17. Gross LJ, McCord RP, LoRE S, Ganusov VV, Hong T, Strickland WC, Talmy D, von Arnim A, Wiggins G (2023). Enhancing Quantitative and Data Science Education for Graduate Students in Biomedical Science. PloS One. Apr 27;18(4):e0284982. doi: 10.1371/journal.pone.0284982.
  18. Groves SM, Panchy N, Tyson DR, Harris LA, Quaranta V, Hong T. Involvement of Epithelial-Mesenchymal Transition Genes in Small Cell Lung Cancer Phenotypic Plasticity. Cancers (Basel). 2023 Feb 25;15(5):1477. doi: 10.3390/cancers15051477.
  19. Gurumoorthy V, Shrestha U, … Smith JC, Petridis L, O’Neill H. Disordered domain shifts the conformational ensemble of the folded regulatory domain of the multidomain oncoprotein c-Src. Biomacromolecules. 24, 2, 714–723 (2023).
  20. Lee G, Zeng K, Duffy CM, Sriharasha Y, Yoo S, Park JH. 2023. In vivo characterization of the maturation steps of PDF neuropeptide precursor in the Drosophila circadian pacemaker neurons. Genetics, in press. doi: 10.1093/genetics/iyad118
  21. Li H, McCord RP. Actin up: shifting chromosomes toward repair, but also translocations. Nat Struct Mol Biol. 2023 Jan;30(1):2-4. doi: 10.1038/s41594-022-00906-4. PubMed PMID: 36577921.
  22. Li J, Xie J …. Smith JC, Hong L. Non-ergodicity of a globular protein extending beyond its functional timescale. Chemical Science. 13 (33), 9668-9677 (2022).
  23. Liang, L, Wang Y …. Smith JC ….. O’Neill H, Davison BH, Raguskas AJ. Chemical and Morphological Structure of Transgenic Switchgrass Organosolv Lignin Extracted by Ethanol, Tetrahydrofuran, and -Valerolactone Pretreatments. ACS Sustainable Chemistry and Engineering. 10 (28), 9041-9052 (2022).
  24. Liu J, Willems HME, Sansevere EA, Allert S, Barker KS, Lowes DJ, Dixson AC, Xu Z, Miao J, DeJarnette C, Tournu H, Palmer GE, Richardson JP, Barrera FN, Hube B, Naglik JR, Peters BM. A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis. PLoS Pathogens (2021) e1009884. doi: 10.1371/journal.ppat.1009884. PMID: 34506615.
  25. Liu S-H,; Xiao S…. Smith JC ….. Loukas P. Identification of Small-Molecule Inhibitors of Fibroblast Growth Factor 23 Signaling via In Silico Hot Spot Prediction and Molecular Docking to α-Klotho Journal of Chemical Information and Modeling. 62 (15), 3627-3637 (2022).
  26. Lokdarshi A and von Arnim AG (2023) A Miniature Sucrose Gradient for Polysome Profiling. Bio-protocol 13: e4622. DOI: 10.21769/BioProtoc.4622.
  27. Lou J, Schuster JA, Barrera FN, Best MD. ATP-Responsive Liposomes via Screening of Lipid Switches Designed to Undergo Conformational Changes upon Binding Phosphorylated Metabolites. J. Amer. Chem. Soc. (2022) ;144(8):3746-3756. PMID: 35171601 DOI: 10.1021/jacs.2c00191.
  28. Luxem K, Sun JJ, Bradley SP, Krishnan K, Pereira TD, Yttri EA, Zimmermann J, Laubach M. “Open-source tools for behavioral video analysis: Setup, Methods and Development”. eLife, 2023.
  29. Mamontov E, Bordalla HN … Smith JC, Sokalov AP. Broadband Wide-Angle VElocity Selector (BWAVES) neutron spectrometer designed for the SNS Second Target Station. EPJ Web of Conferences 272 02003 (2022).
  30. McClintic WT, Scott HL, Moore N, Farahat M, Maxwell M, Schuman CD, Bolmatov D, Barrera FN, Katsaras J, Collier CP. (2023) Heterosynaptic plasticity in biomembrane memristors controlled by pH. MRS bulletin 48 (1), 13-21
  31. Melchionna M.V., Gullett J.M., Bouveret E., Shrestha H.K., Abraham P.E., Hettich R.L., Alexandre G. 2022. Bacterial Homologs of Progestin and AdipoQ Receptors (PAQRs) Affect Membrane Energetics Homeostasis but Not Fluidity. J. Bacteriol. 204(4):e0058321. doi: 10.1128/jb.00583-21.
  32. Miller GM, Ellis A …. Smith JC, Lupu DS. Hypothesis‑Agnostic Network‑Based Analysis of Real‑World Data Suggests Ondansetron is Associated with Lower COVID‑19 Any Cause Mortality. Drugs – RealWorldOutcomes 9 (3), 359-375 (2022).
  33. Mohan M, … Smith JC, Kidder M, Singh S. Accurate Prediction of Carbon Dioxide Capture by Deep Eutectic Solvents using Quantum Chemistry and a Neural Network. Green Chemistry 25(9) 3475 (2023).
  34. Mohan M, Smith MD …. Smith JC. Predictive understanding of the surface tension and velocity of sound in ionic liquids using machine learning. J. Chem. Phys. 158, 214502 (2023).
  35. Mohan M, Smith MD …. Smith JC. Quantum Chemistry-Driven Machine Learning Approach for the Prediction of the Surface Tension and Speed of Sound of Ionic Liquids. ACS Sustainable Chem. Eng. 2023, 11, 20, 7809–7821 
  36. Mongès A, Yaakoub H, Bidon B, Glévarec G, Héricourt F, Carpin S, Chauderon L, Drašarová L, Spichal L, Binder BM, Papon N, Rochange S. (In press) Are histidine kinases of arbuscular mycorrhizal fungi involved in the response to ethylene and cytokinins? Molecular Plant-Microbe Interactions
  37. Mykins M, Layo-Carris D, Dunn L, Skinner DW, Perez S, McBryar A, Shultz TR, Willems A, Lau BYB, Hong T, Krishnan K. “Wild-type MECP2 expression coincides with age-dependent sensory deficits in a female mouse model for Rett syndrome”. Journal of Neuroscience Research, 2023. 
  38. Mykins M, Marrero K, Cataldo G, Aruljothi K, Krishnan K, Brumberg J. “Barrels XXXV: Barrels In-Person”. Somatosensory & Motor Research, 2023. 
  39. Nordick B, Chae-Yeon Park M, Quaranta V, Hong T. Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum. iScience. 2022 Sep 27;25(10):105224. doi: 10.1016/j.isci.2022.105224. 
  40. Panchy N, Watanabe K, Takahashi M, Willems A, Hong T. Comparative single-cell transcriptomes of dose and time dependent epithelial-mesenchymal spectrums. NAR Genom. Bioinform. 2022 Sep 21;4(3):lqac072. doi: 10.1093/nargab/lqac072. 
  41. Park HL, Seo DH, Lee HL, Bakshi A, Park C, Chien Y-C, Kieber JJ, Binder BM, Yoon GM (2023) Ethylene-triggered subcellular trafficking of CTR1 enhances the response to ethylene gas. Nature Communications 124: 365. doi: 10.1038/s41467-023-35975-6.
  42.  Rajeshwart T & Smith JC. Structural Patterns in Class 1 Major Histocompatability Complex-restricted Nonamer Peptide Binding to T-cell Receptors. Proteins: Structure, Function and Bioinformatics. 90(9):1645-1654 (2022).
  43. Roger D, Agarwal R, …. Glaser J, Smith JC. SARS-CoV2 Billion-Compound Docking. Nature Scientific Data. 10(1)173 (2023).
  44. Russell CM, Rybak JA, Miao J, Peters BM, Barrera FN. (2022) The Candida albicans virulence factor candidalysin polymerizes in solution to form membrane pores and damage epithelial cells. Elife 11, e75490.
  45. Russell CM, Rybak JA, Miao J, Peters BM, Barrera FN. (2022) Candidalysin: connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties. Journal of Biological Chemistry, 102829.
  46. Rybak JA, Sahoo AR, Kim S, Pyron RJ, Pitts SB, Guleryuz S, Smith AW, Buck M, Barrera FN. (2023) Allosteric inhibition of the epidermal growth factor receptor through disruption of transmembrane interactions. Journal of Biological Chemistry, https://doi.org/10.1016/j.jbc.2023.104914.
  47. San Martin R, Das P, Sanders JT, Hill AM, McCord RP. Transcriptional profiling of Hutchinson-Gilford Progeria syndrome fibroblasts reveals deficits in mesenchymal stem cell commitment to differentiation related to early events in endochondral ossification. Elife. 2022 Dec 29;11. doi: 10.7554/eLife.81290. PubMed PMID: 36579892.
  48. Schaefer KG, Pittman AE, Barrera FN, King GM. “Atomic force microscopy for quantitative understanding of peptide-induced lipid bilayer remodeling”. Methods (2022) 197:20-29. doi: 10.1016/j.ymeth.2020.10.014.
  49. Shelby SA, Castello-Serrano I, Wisser KC, Levental I, Veatch SL. Membrane phase separation drives responsive assembly of receptor signaling domains. Nat Chem Biol. 2023 Jun;19(6):750-758. doi: 10.1038/s41589-023-01268-8. Epub 2023 Mar 30.
  50. Shelby SA, Shaw TR, Veatch SL. Measuring the Co-Localization and Dynamics of Mobile Proteins in Live Cells Undergoing Signaling Responses. Methods Mol Biol. 2023;2654:1-23. doi: 10.1007/978-1-0716-3135-5_1.
  51. Shelby SA, Veatch SL. The Membrane Phase Transition Gives Rise to Responsive Plasma Membrane Structure and Function. Cold Spring Harb Perspect Biol. 2023 Aug 8:a041395. doi: 10.1101/cshperspect.a041395.
  52. Shen S, Parks JM, Smith JC. HCLus: HLA Class I Supertype Classification. BMC Bioinformatics. 24(1) 1-13 (2023).
  53. Shen S, Parks JM, Smith JC. HLA Class I Supertype Classification Based on Structural Similarity. Journal of Immunology. 210(1) 103-114 (2023).
  54. Sobe R.C., Gilbert C., Vo, L. Alexandre G. and Scharf, B. E. 2022. FliL and its paralog MotF have distinct roles in the stator activity of the Sinorhizobium meliloti flagellar motor. Mol Microbiol 118(3):223-243. doi:10.1111/mmi.14964.
  55. Tan L, Scott H, … Smith JC, Davison J, Elkins J, Nickels J. Amphiphilic co-solvents modulate structure of membrane domains. ACS Sustainable Chemistry & Engineering. 11 4 1598-1609 (2023).
  56. Tan L, Smith MD, Scott H …. Smith JC, Davison BH, Nickels JD. Modeling the partitioning of amphiphilic molecules and co-solvents in biomembranes. Journal of Applied Crystallography. 55(6), 1401-1412 (2022).
  57. Taylor MK, Williams EP, …. Smith JC, Jonsson CBB. Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants. Viruses. 15(3) 611(2023).
  58. Veatch SL, Rogers N, Decker A, Shelby SA. The plasma membrane as an adaptable fluid mosaic. Biochim Biophys Acta Biomembr. 2023 Mar;1865(3):184114. doi: 10.1016/j.bbamem.2022.184114. Epub 2022 Dec 26.
  59. Voloshin R.A., Bozieva A.M., Bruce B.D., and Allakhverdiev S.I. (2023) Photosynthetic microbial fuel cells: practical applications of electron transfer chains. Russian Chem. Reviews, 92:5, 5073; https://doi.org/10.57634/RCR5073.
  60. Willems A, Panchy N, Hong T. Using Single-Cell RNA Sequencing and MicroRNA Targeting Data to Improve Colorectal Cancer Survival Prediction. Cells. 2023 Jan 5;12(2):228. doi: 10.3390/cells12020228.
  61. Workman, C.E., Cawthon, C., Brady, N.G., Bruce, B.D., and Long, B., (2022) Degradation of Esterified Styrene-Maleic Acid Copolymers. Biomacromolecules 23, 11, 4749–4755109; https://doi.org/10.1021/acs.biomac.2c00928.
  62. Xu Y, Kramann R, McCord RP, Hayat S. MASI enables fast model-free standardization and integration of single-cell transcriptomics data. Commun Biol. 6, 465 (2023). doi: 10.1038/s42003-023-04820-3. 
  63. Yao T, Zhang J … Binder BM, …. Chen J-G, Muchero W. (In press) eQTL mapping identified PtrXB38 as a key hub gene in adventitious root development in Populus. New Phytologist.
  64. Zharmukhamedov, S.K., Shabanova, M.S., Huseynova, I.M., Karacan, M.S., Karacan, N., Akar, H., Kreslavski, V.D., Alharby, H.F., Bruce, B.D., and Allakhverdiev, S.I. (2023) Probing the influence of novel organometallic copper (II) complexes on spinach PSII photochemistry using OJIP fluorescence transient measurements. Biomolecules 13(7), 1058; https://doi.org/10.3390/biom13071058.
  65. Zhou, Y., Syed, J., Semchonok, D.A., Kyrilis, F.L., Hamdi, F., Kastrittis, P.L., Wright, E., Bruce, B.D., and Reynolds, T.B. (2023) Solubilization, purification and characterization of the hexameric form of phosphatidylserine synthase from Candida albicans. J. Biol. Chem., 299:6,104756; https://doi.org/10.1016/j.jbc.2023.104756.

Filed Under: newsletter

Updates – 2023

December 1, 2023 by ljudy@utk.edu

Faculty Updates

  • Rachel P. McCord received a College of Arts and Sciences Excellence in Research/Creative Achievement Award and a grant from Science Alliance StART (Support for Affiliated Research Teams).
  • Gladys Alexandre and BCMB were given the 2022 NTID (National Technical Institute for the Deaf at Rochester Institute of Technology) Co-op and Career Center Outstanding Partner Award for involvement in mentoring Deaf and hard-of-hearing students.
  • Albrecht von Arnim will assume a part time (33%) appointment to serve the UT-Oak Ridge Innovation Institute to continue as Director of the Genome Science and Technology graduate program. BCMB faculty have been among the more active in training students in the intercollegiate GST program. The GST program took its place as the third sister program in the Bredesen Center next to the programs in Energy Science and Engineering and Data Science and Engineering.
  • Dan Roberts has retired from UT after over 35 years.
  • Keerthi Krishnan was honored with the Undergraduate Research Mentor of the Year Award from Provost’s Office and an award for Outstanding Graduate Research Mentor from the Graduate Student Senate.

Postdoc and Graduate Student Updates

  • Heng Li (McCord Lab) and Boomer Russell (Barrera Lab) were awarded Graduate Advancement Training and Education (GATE) Fellowships from the Science Alliance.
  • Brandon Estrem (Wang Lab) was given a Division of Biology Cokkinias/Fite Award for Outstanding Scholarly Achievement by a graduate student.
  • Hannah Hughes, postdoc in the Alexandre lab, won best poster by a postdoc at the BLAST (Bacterial Locomotion And Signal Transduction) XVII meeting.
  • Debalina Acharyya (Prosser Lab) won first place in the 3-Minute Thesis (3MT) competition.
  • Morgan House (Joshi Lab) won best post at the FASEB ER structure and function meeting.
  • Boomer Russell (Barrera Lab) received the Graduate Student Senates Award for Excellence in Graduate Research.
  • Mike Mykins was awarded a Herbert Freidberg Nachlas Postdoctoral Fellowship. He also was a college nominee for the Jimmy and Ileen Cheek Graduate Student Medal of Excellence.

Undergraduate Updates

  • Congratulation to undergraduates who won Exhibition of Undergraduate Research and Creative Achievement (EURēCA) awards in the Natural Sciences Division: Vincent Terta, Angela Jo, Benjamin Bridges, Alexandra McBryar, Joseph Martin, Shabre Eskridgé, Raegan van Wirt, Sanaz Hossain, Renata Dos Reis Marques, Christiane Alvarez.
  • Trinity Rose Shultz received an Appalachian Students Promoting the Integration of Research in Education (ASPIRE) scholarship to conduct summer research in the Krishnan lab
  • Breanna Ceesay received a Faculty Research Assistant Fellowship (FRAF) to conduct summer research in the Krishnan lab
  • Joseph Martin was awarded an Advanced Undergraduate Research Activity (AURA), to conduct summer research in the Krishnan lab

Alumni Updates

Jordan Roach (class of 2016) received a UT Volunteer 40 under 40 award during the annual reception.

Congratulations to the 2022-2023 MS and PhD Graduates: Yujie Ye, Amie Sankoh, Mike Mykins, Scott Carlew, Mark Edens, Anwesha Dasgupta.

Filed Under: newsletter

Research News – 2023

December 1, 2023 by ljudy@utk.edu

Fran Barrera

Fighting Candida Virulence

Candida albicans is a fungal human pathogen that causes severe disease by infecting epithelial and immune cells. C. albicans secretes candidalysin, a virulence factor that is required for infection. Candidalysin is a peptide that perforates the lipid membrane that coats cells. This damages the integrity of human cells and initiates the infection process. However, the molecular mechanism that candidalysin uses to form pores is not known, in part due to difficulties in probing interfacial membrane processes with high resolution. 

Research in the Barrera lab has started to get around this problem. Boomer Russell, a graduate student in the Barrera laboratory, is first author on a manuscript published in eLife that unravels how candidalysin works. It turns out that candidalysin uses a molecular mechanism that has never been observed. Against all expectations, candidalysin peptides get together in solution with high affinity, forming a polymer. These polymers close to form loops, which then bind to membranes and form a membrane pore. 
This quite unexpected mechanism is reviewed in an article written by Russell and another graduate student in the lab, Jen Rybak in The Journal of Biological Chemistry. Understanding the candidalysin mechanism will allow for the development of drugs that block its role in fungal infection of humans.



Brad Binder

Ethylene Priming to Grow Bigger and More Stress Tolerant Plants

Ethylene is a gaseous plant hormone that affects plant growth and stress responses. Its practical applications in horticulture, such as ripening bananas, are common knowledge. The Binder lab recently made several advances to understand ethylene signaling. In collaboration with long-time collaborator Eric Schaller at Dartmouth College, they published an article in the Proceedings of the National Academy of Sciences that combines computational and experimental approaches to understand the structural basis for the high affinity binding and signal propagation by ethylene receptors. 

A second collaboration with the lab of Gyeong Mee Yoon at Purdue University published in Nature Communications expands our understanding of the spatiotemporal dynamics involved in ethylene signaling components down-stream of the receptors. Most recently, the Binder lab, in collaboration with Dan Roberts, found that transiently treating germinating seeds with ethylene causes a priming effect leading to large increases in both plant growth and stress tolerance which persist throughout the plants’ lifetime. This discovery, published in PNAS-Nexus, is particularly exciting since growth and stress tolerance usually exhibit an inverse relationship. 

Lead author Eric Brenya, a postdoctoral researcher in the Binder lab, highlights the potential of this finding for horticulture and agriculture: “Given the challenges posed by global warming and diminishing arable land, these discoveries are crucial in sustaining the growing human population.”

The Binder lab is now determining the mechanisms for this priming with funding from a recently awarded NSF grant.



Dynamics of G Protein-Coupled Receptors

G protein-coupled receptors (GPCRs) carry out diverse and important functions and are the target of many therapeutic drugs. The Lamichhane lab continues unraveling the dynamics of GPCRs using single-molecule fluorescence microscopy. 

Recently, they made progress to better understand how GPCRs function by characterizing the dynamics of helix 7 of the human A2A adenosine receptor. These findings, published with graduate student Shushu Wei as lead author in Structure, illustrate that there is a critical intermediate conformational state that has been missed in the currently available structures of this receptor. They also showed that the conformational dynamics of these receptors are temporally ordered, which has implications for understanding how agonists and antagonists affect these receptors and could lead to better drug design to target these receptors. They also have made progress in understanding the dynamics of the extracellular domain of the glucagon receptor, which is important in carbohydrate homeostasis. 
Their findings, detailed in Journal of Biological Chemistry, provide information for the development of therapeutics for diabetes and underscores the lab’s commitment to advancing our knowledge of molecular interactions and conformational changes of these important receptors. These studies were made possible because of an R35 Maximizing Investigators’ Research Award from NIH to Lamichhane.



Seedling

Nature’s Artistry: Exploring the Mesmerizing World of Plant Shapes and Forms

From towering trees with sprawling canopies to delicate vines that elegantly entwine, from the intricate geometry of fern fronds to the symmetrically layered petals of a flower, the diversity in plant shapes is truly captivating. 

All above-ground organs of plants originate from the shoot apical meristem (SAM), a group of undifferentiated stem cells located between the cotyledons of an embryo and later at the apex of a plant’s stem. Even though cells are constantly growing and dividing, the size of the SAM remains unchanged throughout development due to a tight balance between cell proliferation and incorporation of cells into forming organs. 

Researchers in the Shpak lab study cell-cell communications in the SAM. Recently, they uncovered that two signaling pathways are necessary to promote the differentiation of organs in the periphery of the SAM. This research, published in Development, shows that when these signaling pathways are nonfunctional, the SAM grows bigger and bigger but never can form stems, leaves, and flowers. The pathways inhibit the expression of a transcription factor that promotes stem cell identity.
More recent research from the Shpak lab published in Plant Physiology indicates that there is a complex interplay between auxin and other signaling pathways to regulate SAM. Currently, members of the lab are studying signaling that promotes the initiation of leaves and regulates the shape of flowers and the formation of ovules. This work will help us to uncover the molecular mechanisms responsible for the kaleidoscope of plant shapes and forms.



Filed Under: newsletter

BCMB Alumna Makes News – 2023

December 1, 2023 by ljudy@utk.edu

Former BCMB graduate student Amie Sankoh (PhD ’23) gave the commencement address for the Spring 2023 ceremony. Sankoh’s life story is one of determination and focus. She grew up Deaf during the civil war in Sierra Leone, where she had to overcome many barriers including communication.

Research and STEM opportunities are extremely rare for Deaf individuals, yet she earned a science degree at the Rochester Institute of Technology prior to entering the doctorate program in Biochemistry & Cellular and Molecular Biology at UT. Here she studied the role of hormones in plant-pathogen interactions in the lab of Tessa Burch-Smith. Last year, Sankoh made news when she became the first Deaf Black woman to earn a STEM doctorate. 


Filed Under: newsletter

New Faculty Spotlight: Sarah Shelby

December 1, 2023 by ljudy@utk.edu

Sarah Shelby headshot

Assistant Professor Sarah Shelby has long been fascinated by biology. 

“Even back in my years as an undergraduate chemistry major, I was a little bit in awe of the complexity found in biological systems, and have been deeply curious about how complex structures in the cell are fundamentally shaped by basic chemical and physical forces,” she said.

Shelby did her PhD at Cornell University, where she took advantage of a new form of fluorescence microscopy called “super-resolution microscopy.” This method can resolve structures in intact cells as small as 10–20 nanometers, which is ten times smaller than what is possible with conventional fluorescence microscopy. The ability to “see” features so small provided access to the inner workings of complex cellular structures like the plasma membrane, and a new avenue to understand how cells sense and respond to cues from their environment.

“I first used this method in my PhD work to image clustering and dynamics of the IgE receptor, which is the immune receptor in mast cells responsible for allergic responses,” said Shelby.

As a postdoc at the University of Michigan she focused on how interactions between lipids organize plasma membrane components, and how membrane organization impacts signal transduction from cell surface receptors. Lipid-lipid interactions are fascinating because even though they tend to be relatively weak and non-specific compared to interactions between proteins, collectively they lead to non-uniform mixing of the “2D fluid” of the plasma membrane, including its constituent proteins. This effectively compartmentalizes signaling biochemistry on the membrane surface in a similar way that organelles compartmentalize different cellular functions.

“Using super-resolution microscopy, I was able to directly image lipid domains around B cell receptors and show that these domains concentrate key receptor signaling partners in a way that promotes signal transduction,” she said.

She is extending this research at UT.

“I am studying a new receptor system, known as Chimeric Antigen Receptors or CARs,” said Shelby. “CARs are part of a new class of immunotherapy treatments where immune receptors are engineered to direct the immune system to fight cancer. I’m very interested to see if we can use what we know about how plasma membrane structure and organization regulates native immune receptors to investigate how CARs trigger immune responses, and even come up with strategies for how CARs can be improved. We will use super-resolution microscopy to visualize CAR signaling interactions in the plasma membranes of live cells during the initiation of the cellular response.”

Since arriving at UT, she has been building a super-resolution microscope. This is an entirely custom instrument and will be put together as a team effort between Shelby and students in the lab.

“The microscope will be our main experimental tool and I’m excited about involving students in the process because this kind of hands-on experience will give them an opportunity to learn how it works from the bottom up,” she said. “This way, we’ll be in a great position to execute on new ideas and applications for super-resolution microscopy, and push the limits of what the technique is capable of.”

Research in the Shelby lab is interdisciplinary and students will use methods based in a variety of fields including cell biology, biochemistry, biophysics, optics and instrumentation, and quantitative image analysis. 

Shelby joined BCMB in February 2023 and is team-teaching BCMB 401 (Biochemistry 1) this fall. Outside the lab and classroom, she is an avid hiker and camper and is looking forward to exploring the Smokies. She also enjoys cooking, gardening, and biking around town.

Filed Under: newsletter

Understanding Brain Development and How It Can Go Wrong

December 1, 2023 by ljudy@utk.edu

Logan Dunn was initially not interested in science.

“I was a teenager who had zero percent interest in science in general,” he said. “After graduating from high school, I chose what I consider to be the best route for someone who had no idea what they wanted to do with their life: the military. I was a medic in the US Army for seven years. After serving four years on active duty, I chose to come home and use the GI Bill to attend college. I initially wanted to go to medical school, but this changed about five weeks into my first semester. My first science class with an associated lab was General Chemistry I, and I loved my time in lab. I developed great relationships with my professors at Pellissippi State Community College.”

After graduating summa cum laude with an AS in biology from Pellissippi State, Dunn transferred to Maryville College to obtain a BS in biochemistry. During this time, he also participated in the Biophysics NSF REU program hosted at Clemson University, where he used confocal, hyperspectral, and multiphoton imaging modalities to evaluate the cellular uptake and biocompatibility of single-walled carbon nanotube imaging probes. 

While at Maryville College his advisor, Professor Angela Gibson—who obtained her PhD from BCMB—suggested Dunn apply to the BCMB graduate program.

“I chose to join BCMB because I felt like BCMB had all of the tools for science,” he said. “I also enjoyed my interviews with faculty during the recruitment process.”

Dunn arrived at UT with an interest in neurobiology.

“As a teenager, my maternal grandmother was diagnosed with Alzheimer’s disease, and this was a progressively horrible experience for my family,” he said. “When I came here to interview for BCMB, I was interested in working with Professor Keerthi Krishnan, who studies a neurodevelopmental disorder called Rett Syndrome. While a different disorder/disease, my perspective is graduate school is a means to an end—meaning we are here to gain the skills and learn the techniques to ultimately go off into the sunset and do the things we really want to do. Professor Krishnan and I hit it off in my initial interview and during my rotation. I really enjoyed my time in the lab as well as the people in it. And here I am 2½ years later in the Krishnan lab.”

Dunn is currently working on purifying a protein, MeCP2, from female mouse brains that is linked to Rett Syndrome. He plans on analyzing MeCP2 for post-translational modifications using mass spectrometry. Studies on neural activity-dependent post-translational modifications are typically carried out on cultured neurons. Carrying out this research in brains will be challenging, but rewarding because it will help to answer what controls Rett Syndrome. Dunn was awarded a prestigious grant from the NSF Graduate Research Fellowships Program to carry out this research. 

“This fellowship has allowed me to focus on research without having to balance time between lab work and teaching,” he said. “Since being awarded the fellowship, I’ve published one first-author paper with a second manuscript in the final stages of publication.”

When not in the lab, Dunn takes care of his Bernese Mountain Dog, two cats, and two Holland Lop rabbits: “All of which I just found out I’m allergic to.”

Filed Under: newsletter

How Cells Store Fat

December 1, 2023 by ljudy@utk.edu

Morgan House originally planned on attending medical school. But, her undergraduate research experience at UT in the lab of Professor Mariano Labrador made her realize she had a passion for research. 

“I have always been interested in science, asking questions, and problem solving,” said House. “As I grew up, I watched many of my family members suffer from cancer and disease. I wanted to help somehow, and I thought that becoming a medical doctor was a way I could make a difference. During undergraduate school, I became aware of other job opportunities in science such as a research scientist. After spending time in my undergraduate research lab conducting experiments and generating data, I realized that going to graduate school would be the best fit for me and my future goals.”

Once she joined the BCMB graduate program, House chose very different areas of research for her rotations: microbiology, plant biology, and cell biology. She ended up joining the cell biology lab of Professor Amit Joshi where she is studying organelle biogenesis from the endoplasmic reticulum membrane. 

“I joined this lab for a few reasons, one being microscopy,” she said. “I really enjoy being able to see what is happening in cells in real time. Another reason I was interested in the Joshi Lab is because of the implications of our research in human health. My research is centered around understanding how cells store fat in the form of lipid droplets using baker’s yeast as the model organism. With obesity and metabolic disorders being major health issues in the US, it is important to understand how excess fat is stored and utilized by the body. I hope that one day my research may have an impact on those suffering from these conditions.”

House recently presented her research at the Federation of American Societies for Experimental Biology (FASEB) Endoplasmic Reticulum conference in Melbourne, Florida. She was asked to give a talk based on her poster and won a best poster award. 

“This experience gave me some new friends and contacts, and furthermore gave me confidence in myself as a researcher,” she said. “One of the best parts of BCMB is the community that we have. I always feel like I have someone to reach out to if I need help with my research or with personal problems. I think we are very collaborative and have a community that feels like a family.”

In her spare time, House enjoys collecting and caring for her houseplants and outdoor plants, playing the piano, and singing. She also loves Vol sports, so you can always catch her watching a game and sometimes attending them.

Filed Under: newsletter

Dan Roberts retires after 36 years at UT

December 1, 2023 by ljudy@utk.edu

Professor Dan Roberts, who arrived at UT in 1987, retired in December of last year. His internationally recognized research program focused on several aspects of plant biology, including the role of calcium signaling, abiotic stress responses, the biology of root nodules, aquaporins and related transporters, and RNA homeostasis. 

Past researchers in his lab note that Roberts was a rigorous mentor who taught them many important lessons on how to be a scientist. As his first lab technician John Cobb (now professor at the University of Calgary) noted, “From a science perspective, I would say I really learned the importance of scientific rigor from Dan and I still carry many lessons from him into how I manage my own lab here in Calgary. I try to channel a bit of Dan when I tell one of my students how things should be done.” 

Dan Roberts with early members of the lab.

Roberts was also very active in undergraduate education, in particular taking the lead in designing and implementing core BCMB classes. He is probably remembered by many undergraduates as the instructor of the infamous BCMB 401 (Biochemistry 1) taken by BCMB majors and pre-health students. Roberts made many contributions to our department as a faculty member and department head and in the last few years ran our highly successful, NSF-sponsored research experience for Deaf and hard-of-hearing undergraduates. In retirement he is finishing up several manuscripts from the lab, spending more time with family, and playing the bass guitar. 

Filed Under: newsletter

Message from the Department Head – 2023

December 1, 2023 by ljudy@utk.edu

Headshot

Big ideas and the drive to understand the world around us motivate research endeavors. In this issue of the newsletter, we introduce you to several of the big ideas pursued by departmental faculty and their students. You will read about recent findings from some of the groups within the research breadth housed in the department. Basic research paves the way for discoveries that could become solutions to the world’s most pressing problems. Some of BCMB’s researchers’ big ideas that you will read about in this newsletter address the most challenging issues of our times: human health and crop resilience and productivity to meet growing demands for food in a changing climate. I trust reading about ongoing research in BCMB will inspire you to connect with us and share your own big ideas. 

Associate Professor Barrera and his research team have made recent progress deciphering the molecular mechanisms of a virulence factor produced by the fungal pathogen Candida albicans, a peptide aptly named candidalysin. Using single-molecule fluorescence microscopy, a powerful approach to decipher molecular dynamics in biological macromolecules, Assistant Professor Lamichhane’s laboratory is continuing to break barriers in our understanding of molecular mechanisms of GPCR receptors, including understudied representative members of this large group of proteins that are prime pharmaceutical drug targets. Our newly recruited Assistant Professor Sarah Shelby is also using super-resolution microscopy to address lipid-membrane receptors interactions in receptors of the immune system, with this research having broad and potentially transformative applications to human health and the development of new therapies. One example of such application that you will read about below is regarding her plans to characterize Chimeric Antigen Receptors, or CARs, that are considered promising in cancer immunotherapies applications. 

Food is a prerequisite to human health: basic plant biology research can’t be unentangled from human welfare. In this newsletter, you will read about recent findings in Professor Binder’s laboratory and his team that highlight how a plant hormone ethylene, may modulate plant resilience to stress. I also invite you to read about Professor Shpak’s laboratory research that uncovers fundamental mechanisms of plant development that could be used to enhance plant productivity, including fruit production.

I believe that there are no big ideas or research leadership outside of a demonstrated commitment to training the next generation of students, whether they become scientists or not. In this newsletter, you will read about the talented next generation of scientists BCMB is helping train. These include graduate students Morgan House and Logan Dunn, as well as the amazing Amie Sankoh, the first Deaf Black woman to earn a STEM doctorate and graduate from BCMB. 

Last but certainly not least, I want to recognize my colleague and predecessor, Professor Emeritus Dan Roberts, who officially retired from UT and BCMB in December 2022 after over 35 years of outstanding service, including as a department head for 2013-2018. I hope you enjoy reading about Dan’s new hobbies and get in touch with any story you would like to share with us. 

As always: please, keep in touch!

Gladys Alexandre, Professor and Head

Filed Under: newsletter

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