Document text
Principal Investigator: Jeffrey Reece
Organization: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
Fiscal Year: 2024
Award: $498,613
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
The mission of the National Institutes of Health (NIH) is to seek fundamental knowledge about the nature and behavior of living systems and to apply that knowledge to enhance health, lengthen life, and reduce illness and disability.
As part of the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Intramural Research Program (IRP) conducts biomedical research and training related to diabetes mellitus; endocrine, bone, and metabolic diseases; digestive diseases, including liver diseases and nutritional disorders; and kidney, urologic, and hematologic diseases. Intramural research is conducted in the Institute's laboratories and clinical facilities in Bethesda, Maryland and in Phoenix, Arizona. There are currently 18 Laboratories and Branches (i.e. 18 departments with different focus areas) in the NIDDK IRP. Most if not all of these areas of research, either occasionally or on an ongoing basis, require light microscopy (LM) methods to qualitatively complement other assays, or as the basis of a quantitative assay.
There are three main categories of LM. Conventional widefield, transmitted light techniques, such as darkfield or differential interference contrast (DIC), are still useful because of their innate ability to show cellular morphology. Second, an old standby, immunohistochemistry (IHC)-- using absorptive probes to colorize tissue in transmitted light-- has been used for decades (e.g. in pathology), but recent advances with new probes and color deconvolution have allowed the field to grow, although requiring more finesse when being quantitated.
The third and most common category of LM is characterized by the use of fluorescent probes targeting biomolecules (specific proteins, DNA, etc) of interest, making them glow with different colors on a black background. Such fluorescent dyes can even be used to monitor subcellular events in real-time. There are many sub-categories of fluorescence microscopy, e.g. confocal, super-resolution, and TIRF (Total Internal Reflectance-induced Fluorescence). Each of these involve specialized technique in sample prep, image acquisition, and/or image analysis.
Some NIDDK labs might be comfortable without advanced help on one of more of the techniques described above, and might also be able to set aside a budget for equipment they would use regularly; but to fill any gaps, the NIDDK Advanced Light Microscopy & Image Analysis Core (ALMIAC) remains a reliable resource for cutting-edge light microscopy equipment, software, and expertise.
For the FY2024 budget year (October 2023 - September 2024), there were >65 researchers using ALMIAC resources, representing at least 28 (out of 96, 29%) "Sections" (individual labs), from at least 12 (out of 18, or 67%) Laboratories and Branches.
Out of the 65+ individual researchers helped, there were at least 9 NIDDK publications during FY 2024 (and several more in preprint stage as of 9/3/2024, not listed below) that used images acquired and/or analyzed with the help of ALMIAC resources:
--Peng Wang, D Eric Anderson, Yihong Ye. PI3K-AKT activation resculpts integrin signaling to drive filamentous tau-induced proinflammatory astrogliosis. Cell Biosci. 2023 Sep 27;13(1):179. PMID: 37759245 PMCID:PMC10536728 DOI:10.1186/s13578-023-01128-x
--Qi Zhang, Weichun Tang, Eduardo Stancanelli, Eunkyung Jung, Zulfeqhar Syed, Vijayakanth Pagadala, Layla Saidi, Catherine Z. Chen, Peng Gao, Miao Xu, Ivan Pavlinov, Bing Li, Wenwei Huang, Liqiang Chen, Jian Liu, Hang Xie, Wei Zheng, and Yihong Ye. Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation. Nat Commun. 2023; 14: 5777. PMID: 37723160 PMCID:PMC10507024 DOI:10.1038/s41467-023-41453-w
--Gabriella Quinn, Rabab O. Ali, Grace Y. Zhang, Kareen Hill, Elizabeth Townsend, Regina Umarova, Moumita Chakraborty, Maleeha F. Ahmad, Meital Gewirtz, James Haddad, Sergio Rosenzweig, Shakuntala Rampertaap, Megan Schoenfeld, Shanna Yang, Christopher Koh, Elliot Levy, David E. Kleiner, Ohad Etzion, Theo Heller. Non-selective dampening of the host immune response after hepatitis C clearance and its association with circulating chemokine and endotoxin levels. Liver Int. 2023 Dec;43(12):2701-2712. PMID:37752797 DOI:10.1111/liv.15737.
--Antwi-Boasiako Oteng, Srinivas Pittala, Andrea Kliewer, Yishu Qiu and Jürgen Wess. Hepatic GRK2 is dispensable for glucose homeostasis and other key metabolic parameters in mice. Mol Metab. 2024 Jan:79:101866. doi: 10.1016/j.molmet.2023.101866. Epub 2023 Dec 28.
--Liu Liu, Kimberley EI, Diptadip Dattaroy, Luiz F. Barella, Yinghong Cui, Sarah M. Gray, Carla Guedikian, Min Chen, Lee S. Weinstein, Emily Knuth, Erli Jin, Matthew J. Merrins, Jeffrey Roman, Klaus H. Kaestner, Nicolai Doliba, Jonathan E. Campbell & Jürgen Wess. Intra-islet α-cell Gs signaling promotes glucagon release. Nat Commun. 2024 Jun 15;15(1):5129. doi: 10.1038/s41467-024-49537-x.
--Clio Hockens, Hernan Lorenzi, Tricia T Wang, Elissa P Lei, Leah F Rosin. Chromosome segregation during spermatogenesis occurs through a unique center-kinetic mechanism in holocentric moth species. PLoS Genetics. 2024 Jun 24;20(6):e1011329. doi: 10.1371/journal.pgen.1011329.
--Ye Liu, Lily Ng, Hong Liu, Heike Heuer, Douglas Forrest. Cone photoreceptor differentiation regulated by thyroid hormone transporter MCT8 in the retinal pigment epithelium. Proc Natl Acad Sci U S A. 2024 Jul 23;121(30):e2402560121. doi: 10.1073/pnas.2402560121.
--Khun Zaw Latt, Teruhiko Yoshida, Shashi Shrivastav, Amin Abedini, Jeff M Reece, Zeguo Sun, Hewang Lee, Koji Okamoto, Pradeep Dagur, Yu Ishimoto, Jurgen Heymann, Yongmei Zhao, Joon-Yong Chung, Stephen Hewitt, Pedro A Jose, Kyung Lee, John Cijiang He, Cheryl A Winkler, Mark A Knepper, Tomoshige Kino, Avi Z Rosenberg, Katalin Susztak, Jeffrey B Kopp. Single-Nucleus RNA Sequencing Reveals Loss of Distal Convoluted Tubule 1 Renal Tubules in HIV Viral Protein R Transgenic Mice. Am J Pathol
. 2024 Jul 18:S0002-9440(24)00237-2. doi: 10.1016/j.ajpath.2024.06.006.
--Qi Zhang, Meng Liu, Yue Xu, Juhyung Lee, Brothely Jones, Bing Li, Wenwei Huang, Yihong Ye & Wei Zheng. Tilorone mitigates the propagation of α-synucleinopathy in a midbrain-like organoid model. J Transl Med. 2024 Sep 2;22(1):816. doi: 10.1186/s12967-024-05551-7.
In addition to helping with specific research projects, several areas of improvement in capability and workflow include:
1) Addition of one (inherited) microscope into the ALMIAC: a Zeiss LSM 710 confocal microscope, the first ALMIAC instrument in building 10 (NIH Clinical Center).
2) Addition of camera-based slide/tissue scanner using parts of older systems.
3) First meeting of the ALMIAC's Core Advisory Group.
Terms: <1-Phosphatidylinositol 3-Kinase><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><3-D><3-Dimensional><3D><ACE2><ADRBK1><ADRBK1 gene><AKT><Akt protein><Alpha Cell><Antidiabetic Hormone><Area><Arizona><Assay><BARK1><Behavior><Beta-ARK-1><Bioassay><Biological Assay><Biomedical Research><Blood Diseases><Body Tissues><Bone Diseases><Budgets><COVID-19 virus><COVID19 virus><Categories><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Cellular Morphology><Ch'i><Chemotactic Cytokines><Chromosome Segregation><Clinical><CoV-2><CoV2><Color><Complement><Complement Proteins><Computer software><Computers><Cone Photoreceptors><DNA><Darkness><Deoxyribonucleic Acid><Development><Diabetes Mellitus><Digestive Diseases><Digestive System Diseases><Digestive System Disorders><Distal Convoluted Tubule><Distal Kidney Tubules><Distal convoluted renal tubule structure><Endocrine Diseases><Endocrine Diseases and Manifestations><Endocrine System Diseases><Endotoxins><Equipment><Event><Fluorescence><Fluorescence Agents><Fluorescence Light Microscopy><Fluorescence Microscopy><Fluorescent Agents><Fluorescent Dyes><Fluorescent Probes><GI tract disorder><GRK2><Genetic><Giant Cells><Glucagon><Glucagon Cell><Glucagon Secreting Cell><Glukagon><HCV infection><HG-Factor><HIV Viral Protein R><HIV vpr Gene Product><HIV-1 vpr Gene Products><Health><Hematologic Diseases><Hematological Disease><Hematological Disorder><Heparan Sulfate><Heparitin Sulfate><Hepatic><Hepatic Disorder><Hepatitis C><Hepatitis C virus infection><Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted><Hepatitus C><Hereditary><Homologous Chemotactic Cytokines><Hyperglycemic-Glycogenolytic Factor><Illumination><Image><Image Analyses><Image Analysis><Immune response><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Immunological response><Individual><Inflammatory><Inherited><Integrins><Integrins Extracellular Matrix><Intercrines><Intracellular Communication and Signaling><Intramural Program><Intramural Research><Intramural Research Program><Investigators><Journals><Kidney Diseases><Kidney Tubules><Kinetics><Knowledge><Laboratories><Laser Electromagnetic><Laser Radiation><Lasers><Licensing><Life><Lighting><Lilium><Lily><Liver><Liver diseases><MT-bound tau><Magazine><Maryland><Mesencephalon><Metabolic><Metabolic Diseases><Metabolic Disorder><Methods><Mice><Mice Mammals><Microscope><Microscopy><Mid-brain><Midbrain><Midbrain structure><Mission><Modeling><Monitor><Moths><Multinucleated Giant Cells><Murine><Mus><NIDDK><NIH><National Institute of Diabetes and Digestive and Kidney Diseases><National Institutes of Health><Nature><Nephropathy><Nutrition Disorders><Nutritional Disorders><Organism><Organoids><Outer pigmented layer of retina><PI-3 Kinase><PI3-Kinase><PI3CG><PI3KGamma><PI3k><PIK3><PIK3CG><PIK3CG gene><Pathology><Phosphatidylinositol 3-Kinase><Phosphatidylinositol-3-OH Kinase><Phosphoinositide 3-Hydroxykinase><Pigment cell layer of retina><Pigmented layer of retina><Polykaryocytes><Preparation><Printing><Protein Kinase B><Proteins><Proto-Oncogene Proteins c-akt><PtdIns 3-Kinase><Publications><Qi><R Gene Products><R-Series Research Projects><R01 Mechanism><R01 Program><RAC-PK protein><Renal Disease><Renal tubule structure><Research><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Resources><Retinal Cone><Retinal Pigment Epithelium><Retinal pigment epithelial cells><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SIS cytokines><Sampling><Scanning><Scientific Publication><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Side><Signal Transduction><Signal Transduction Systems><Signaling><Single-Nucleus Sequencing><Slide><Software><Spermatogenesis><Structure><Structure of retinal pigment epithelium><Subcategory><Syncytium><System><Techniques><Technology><Thesaurismosis><Thyroid Gland Hormone><Thyroid Hormones><Time><Tissues><Training><Transgenic Mice><Type I Phosphatidylinositol Kinase><Type III Phosphoinositide 3-Kinase><Tzanck Cell><United States National Institutes of Health><Urinary Tract Diseases><Urologic Diseases><Urologic Disorder><Urological Diseases><Urological Disorders><Wuhan coronavirus><absorption><alpha-cell><angiotensin converting enzyme 2><angiotensin converting enzyme II><astrogliosis><biological signal transduction><blood disorder><blood glucose regulation><bone disorder><c-akt protein><cell morphology><chemoattractant cytokine><chemokine><chromosome division><clinical center><colophony><complementation><cone cell><coronavirus disease 2019 virus><coronavirus disease-19 virus><developmental><diabetes><digestive disorder><digestive tract disease><disability><endocrine disorder><equipment acquirement><equipment acquisition><equipment investment><equipment procurement><equipment purchase><equipment purchasing><experience><finesse><fluorescent dye/probe><gastrointestinal tract disease><gastrointestinal tract disorder><glucose control><glucose homeostasis><glucose regulation><hCoV19><hep C><hepatic body system><hepatic disease><hepatic organ system><hepatitis non A non B><hepatopathy><host response><image evaluation><image interpretation><imaging><immune system response><immunoresponse><improved><infection by hepatitis c virus><instrument><instrument acquisition><instrument investment><instrument procurement><instrument purchase><interest><islet><kidney disorder><light microscopy><light transmission><liver disorder><living system><meeting><meetings><metabolism disorder><microtubule bound tau><microtubule-bound tau><nCoV2><non A, non B hepatitis><non-A, non-B hepatitis><preparations><proto-oncogene protein RAC><proto-oncogene protein akt><rac protein kinase><rap Gene Products><related to A and C-protein><renal disorder><renal tubule><rosin><sNuc-Seq><service providers><single nucleus RNA-sequencing><single nucleus seq><single-nucleus RNA-seq><snRNA sequencing><snRNA-seq><super high resolution><superresolution><synucleinopathy><tau><tau Proteins><tau factor><technology/technique><three dimensional><tool><ultra high resolution><urinary tract disorder><vpr Gene Products><vpr Protein><α-cell><τ Proteins>