| 163 | Ramona Neunuebel, PhD. | <p>Associate Professor <br></p> | (302) 831-3450 | | neunr@udel.edu | 330 Wolf Hall | 334 Wolf Hall | Department of Biological Sciences 105 The Green Room 330 Newark, DE 19716 | <ul>
<li><strong>B.A., M.S.</strong> - Babes-Bolyai University (Romania)
</li><li><strong>Ph.D.</strong> - Texas A&M University
</li><li><strong>Postdoctoral</strong> - National Institute for Child Health and Human Development, National Institutes of Health </li></ul>
<div> </div> | <ul>
<li><strong>BISC 300</strong> - Introduction to Microbiology
</li><li><strong>BISC 850</strong> - Advanced Topics in Host-Microbe Interaction </li></ul> | <p>To survive in eukaryotic cells, intracellular bacteria have evolved complex mechanisms that maintain the delicate balance between exploiting and preserving host cellular resources. Our group investigates the cellular and molecular mechanisms that bacterial pathogens use to survive and replicate inside host cells. Our model system is <em>Legionella pneumophila</em>, a Gram negative bacterium commonly found as an endosymbiont of amoebae in fresh water and soil. <em>L. pneumophila</em> is also an opportunistic pathogen and infects human alveolar macrophages upon inhalation of contaminated aerosols causing a severe form of pneumonia known as Legionnaires' disease. <em>L. pneumophila</em> is internalized into host cells by phagocytosis and remains enclosed in a membrane-bound compartment that the pathogen “remodels” in order to escape degradation by the host and support bacterial growth. Over the course of infection, <em>L. pneumophila</em> translocates more than 300 effector proteins into the host cytosol through a specialized secretion system. These effectors manipulate host proteins to subvert eukaryotic cellular pathways. We use a multifaceted approach involving biochemistry, cell biology, and genetics to study two important aspects of infectious disease: eukaryotic pathways targeted during infection and mechanisms that bacterial proteins use to modulate the activity of host proteins.</p> | <p>Both amoebae and macrophages are phagocytic cells and they engulf and destroy microorganisms. Under normal circumstances, the phagosome containing the cargo destined for degradation undergoes maturation through sequential fusion with endocytic compartments and ultimately with the lysosome to destroy its contents. However, <em>L. pneumophila </em>resists degradation in both cell types by blocking phagosome maturation. A current focus in our lab is to determine how <em>L. pneumophila </em>modulates membrane transport pathways of the host cell to derail phagosome maturation.</p>
<p>A striking feature of <em>L. pneumophila</em> is its ability to translocate a vast number of effector proteins into the host cell to subvert the function of key regulatory proteins including Rab GTPases. These proteins act as molecular switches and they are attractive targets for intracellular bacterial pathogens due to the pivotal roles they play in eukaryotic cell function. Rab GTPases are targeted by <em>L. pneumophila</em> effector proteins during infection and our group is pursuing the mechanisms that <em>L. pneumophila</em> uses to manipulate their activity. We focus on determining how <em>L. pneumophila</em> effector proteins control the activity of host small GTPases through post-translational modifications. </p> | <p>
<strong>Graduate students</strong></p><ul><li> Samual Allgood (doctoral)</li><li> Rebecca Noll (doctoral)</li><li> Colleen Pike (doctoral)</li><li> Barbara Romero-Dueñas (doctoral)<br></li></ul>
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<p>
<strong>Undergraduate students</strong></p><ul><li> Andre Cunningham</li><li> Matthew Bott<br></li></ul> | <p>
<strong>Submitted/In review/Revisions</strong></p><p> Allgood SC, Pike CM, Noll RR, Romero BP,
<strong>Neunuebel MR</strong>. Quantifying recycling endocytosis during macrophage infection by Legionella pneumophila.
<strong>Journal of Visual Experimentation</strong>. Submitted</p><p> Pike CM, Noll RR,
<strong>Neunuebel MR</strong>. Exploitation of phosphoinositides by the intracellular pathogen, Legionella pneumophila . In: Pathogenic Bacteria. Kırmusaoğlu S, editor. Online:
<strong>IntechOpen</strong>. Submitted</p>
<br>
<p>
<strong>Published</strong></p><p> Pike CM, Boyer-Andersen R, Kinch LN, Caplan JL, and
<strong>MR Neunuebel</strong>. (2019)
<a href="https://www.ncbi.nlm.nih.gov/pubmed/30733336">
<em>Legionella</em> effector RavD binds phosphatidylinositol-3-phosphate and helps suppress endolysosomal maturation of the Legionella-containing vacuole</a>.<strong>
<em>J. Biol. Chem</em></strong> 294(16):6405-6415.</p><p> Allgood SC and
<strong>MR Neunuebel</strong>. (2018)
<a href="https://www.ncbi.nlm.nih.gov/pubmed/29748997">The recycling endosomes and bacterial pathogens</a>.
<em>Cell. Microbiol.</em> 20(7):1-11.</p><p> Yu X*, Noll RR*, Romero-Dueñas BP, Allgood SC, LaBaer J, Machner MP, Qiu J, and
<strong>MR Neunuebel</strong>. (2018)
<a href="https://www.ncbi.nlm.nih.gov/pubmed/29433439">
<em>Legionella</em> effector AnkX interacts with host nuclear protein PLEKHN1</a>. *Co-first authors;
<strong>
<em>BMC Microbiol.</em></strong> 18(5):1-14.</p><p> Allgood SC*, Romero Dueñas BP*, Noll RR, Pike CM, Lein S, and
<strong>MR</strong>
<strong>Neunuebel</strong>. (2017)
<a href="https://www.ncbi.nlm.nih.gov/pubmed/28944216">
<em>Legionella</em> Effector AnkX Disrupts Host Cell Endocytic Recycling in a Phosphocholination-Dependent Manner</a>. *Co-first authors;
<strong>
<em>Front. Cell. Infect. Microbiol.</em></strong> Sep 8;7:397.</p><p> Yu X, Decker KB, Barker K, Neunuebel MR, Saul J, Graves M, Westcott N, Hang H, LaBaer J, Qiu J, Machner MP.
<a href="https://www.ncbi.nlm.nih.gov/pubmed/25739981/"> Host-pathogen interaction profiling using self-assembling human protein arrays. </a>
<strong>J Proteome Res.</strong> 2015 Apr 3;14(4):1920-36. doi: 10.1021/pr5013015. Epub 2015 Mar 18. PubMed PMID: 25739981; PubMed Central PMCID: PMC4467460. </p><p> Chen Y, Tascón I,
<strong>Neunuebel MR</strong>, Pallara C, Brady J, Kinch LN, Fernández-Recio J, Rojas AL, Machner MP, Hierro A. (2013)
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656104/">Structural basis for Rab1 de-AMPylation by the Legionella pneumophila effector SidD.</a>
<strong>PLoS Pathog.</strong> 9(5):1-14.</p><p>
<strong>Neunuebel MR</strong> and Matthias P Machner. (2012)
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398914/">The taming of a Rab GTPase by
<em>Legionella pneumophila</em></a>.
<strong>Small GTPases </strong>3(1):28-33.</p><p>
<strong>Neunuebel MR</strong>, Mohammadi S, Jarnik M, Machner MP. (2012)
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294832/">
<em>Legionella pneumophila</em> LidA Affects Nucleotide Binding and Activity of the Host GTPase Rab1</a>.
<strong>J. Bacteriol. </strong>194(6):1389-400.</p><p>
<strong>Neunuebel MR</strong>, Chen Y, Gaspar AH, Backlund PS Jr, Yergey A, Machner MP. (2011)
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209958/">De-AMPylation of the small GTPase Rab1 by the pathogen
<em>Legionella pneumophila</em></a>.
<strong>Science</strong> 333(6041):453-6.</p><p> Mella-Herrera RA,
<strong>Neunuebel MR</strong>, Kumar K, Saha SK, Golden JW. (2011)
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133031/">The
<em>sigE</em> gene is required for normal expression of heterocyst-specific genes in Anabaena sp. strain PCC 7120</a>.
<strong>J Bacteriol.</strong> 193(8):1823-32.</p><p> Mella-Herrera RA,
<strong>Neunuebel MR</strong>, and Golden JW. (2010)
<a href="http://mic.sgmjournals.org/content/157/3/617.long">
<em>Anabaena</em> sp. strain PCC 7120
<em>conR </em>contains a LytR-CpsA-Psr domain, is developmentally regulated, and is essential for diazotrophic growth and heterocyst morphogenesis</a>.
<strong>Microbiology</strong> 157: 617 - 626.</p><p>
<strong>Neunuebel MR</strong> and JW Golden. (2008)
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2566204/">The
<em>Anabaena</em> sp. strain PCC 7120 gene all2874 encodes a diguanylate cyclase and is required for normal heterocyst development under high-light growth conditions</a>.
<strong>J. Bacteriol.</strong> 190:6829-6836 </p><p>
<strong>(Neunuebel) Aldea MR</strong>, Kumar K, Golden JW. (2007) Heterocyst development and pattern formation, p. 75-90 In W. C. Winans, and B. L. Bassler (ed.), Chemical communication among bacteria.
<strong>ASM Press</strong>, Washington, DC.</p><p>
<strong>(Neunuebel) Aldea MR</strong>, Mella-Herrera RA, Golden JW. (2007)
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168693/">Sigma factor genes
<em>sigC</em>,
<em>sigE</em>, and
<em>sigG</em> are upregulated in heterocysts of the cyanobacterium Anabaena sp. strain PCC 7120</a>.
<strong>J. Bacteriol. </strong>189:8392-8396. </p><br> | | | <img alt="" src="/Images%20Bios/Portrait_Ramona%20Neunuebel.png" style="BORDER:0px solid;" /> | |
