{"id":762,"date":"2024-12-17T10:28:34","date_gmt":"2024-12-17T15:28:34","guid":{"rendered":"https:\/\/www.golive.clarku.edu\/faculty\/profiles\/jacqueline-dresch\/"},"modified":"2026-04-03T15:07:13","modified_gmt":"2026-04-03T19:07:13","slug":"jacqueline-dresch","status":"publish","type":"cu_faculty","link":"https:\/\/www.clarku.edu\/faculty\/profiles\/jacqueline-dresch\/","title":{"rendered":"Jacqueline Dresch"},"content":{"rendered":"<p><span>Jackie Dresch received a B.A from SUNY Geneseo in 2006, and a Ph.D. in Mathematics and Quantitative Biology from Michigan State University in 2012.\u00a0 She has been at Clark since 2015.<\/span><\/p>\n<p>Professor Dresch\u2019s research focuses on modeling transcriptional regulation in fruit flies (Drosophila melanogaster).\u00a0 She is interested in many topics at the interface of mathematics and biology, including reaction-diffusion equations, numerical solvers, sensitivity analysis, parameter estimation, image processing, and bioinformatics.<\/p>\n<p>Professor Dresch enjoys teaching a wide range of Mathematics courses, including Calculus, Linear Algebra, Differential Equations, Numerical Analysis, and Mathematical Biology.<\/p>\n","protected":false},"author":0,"featured_media":1858,"parent":0,"template":"","meta":{"cu_faculty_f180_userid":"C70231168","cu_faculty_first_name":"Jacqueline","cu_faculty_last_name":"Dresch","cu_faculty_employment_status":"Full Time","cu_faculty_rank":"Associate Professor","cu_faculty_position":"Associate Professor","cu_faculty_phone":"","cu_faculty_email":"JDresch@clarku.edu","cu_faculty_location":"","cu_faculty_about":"<p><span>Jackie Dresch received a B.A from SUNY Geneseo in 2006, and a Ph.D. in Mathematics and Quantitative Biology from Michigan State University in 2012.\u00a0 She has been at Clark since 2015.<\/span><\/p>\n<p>Professor Dresch\u2019s research focuses on modeling transcriptional regulation in fruit flies (Drosophila melanogaster).\u00a0 She is interested in many topics at the interface of mathematics and biology, including reaction-diffusion equations, numerical solvers, sensitivity analysis, parameter estimation, image processing, and bioinformatics.<\/p>\n<p>Professor Dresch enjoys teaching a wide range of Mathematics courses, including Calculus, Linear Algebra, Differential Equations, Numerical Analysis, and Mathematical Biology.<\/p>","cu_faculty_degrees":"<span>Ph.D. in Mathematics and Quantitative Biology,<\/span> Michigan State University, 2012\n<span>B.S. in Mathematics,<\/span> SUNY Geneseo, 2006","cu_faculty_cv":"https:\/\/faculty180.interfolio.com\/public\/download.php?key=SDRwNCtxSUpsamxBQ213WS9ucHFuNnMwT0hzQU11b2RPQkJ2cWc3amxyUmNRdVVXTkF4MU1zT21qREtJZEdWZ1pRbW1uQVRUQUM2K0wzS0pPd2I2eW5yTW5UelBYbjlvczRyb1hCR2xaSS9CT3c2Vk5iOWlicUlFdUpMWXM5VlU%3D","cu_faculty_links":"[]","cu_faculty_scholarly_interests":"","cu_faculty_scholarly_works":"[{\"activityid\":7647,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"&lt;p&gt;&lt;strong&gt;&lt;a href=&quot;https:\\\/\\\/academic.oup.com\\\/genetics\\\/article\\\/229\\\/1\\\/1\\\/7912301?login=false&amp;utm_source=advanceaccess&amp;utm_campaign=genetics&amp;utm_medium=email&quot;&gt;Two coacting shadow enhancers regulate &lt;em&gt;twin of eyeless &lt;\\\/em&gt;expression during early\\u00a0&lt;em&gt;Drosophila &lt;\\\/em&gt;development.&lt;\\\/a&gt;&lt;\\\/strong&gt;&lt;br&gt;&lt;span style=&quot;font-size:medium;&quot;&gt;&lt;\\\/span&gt;&lt;\\\/p&gt;\",\"Journal Title\":\"Genetics\",\"Series Title\":\"\",\"Month \\\/ Season\":\"\",\"Year\":2025,\"Publisher\":\"\",\"Publisher City and State\":\"\",\"Publisher Country\":\"\",\"Volume\":\"229\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"1-43\",\"ISSN\":\"\",\"DOI\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":7647,\"status\":\"Completed\\\/Published\",\"term\":\"Summer\",\"year\":2024,\"termid\":\"2023\\\/05\",\"listingorder\":6,\"completionorder\":6},{\"id\":7647,\"status\":\"Submitted\",\"term\":\"Spring\",\"year\":2024,\"termid\":\"2023\\\/03\",\"listingorder\":2,\"completionorder\":2},{\"id\":7647,\"status\":\"Submitted\",\"term\":\"Summer\",\"year\":2023,\"termid\":\"2022\\\/05\",\"listingorder\":2,\"completionorder\":2},{\"id\":7647,\"status\":\"In Progress\",\"term\":\"Spring\",\"year\":2023,\"termid\":\"2022\\\/03\",\"listingorder\":1,\"completionorder\":1}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline M. Dresch\",\"Luke L. Nourie\",\"Regan D. Conrad\",\"Lindsay T. Carlson\",\"Elizabeth I. Tchantouridze\",\"Biruck Tessema\",\"Eleanor Verhagen\",\"Mahima Gupta\",\"Diego Borges-Rivera\",\"Robert A. Drewell\"],\"sort_date\":\"2025-1-01\"},{\"activityid\":13477,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Experimental approaches to investigate biophysical interactions between homeodomain transcription factors and DNA\",\"Journal Title\":\"Biochimica et biophysica acta. Gene regulatory mechanisms\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2025,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"1868\",\"Issue Number \\\/ Edition\":\"1\",\"Page Number(s) or Number of Pages\":\"195074\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"Homeodomain transcription factors (TFs) bind to specific DNA sequences to regulate the expression of target genes. Structural work has provided insight into molecular identities and aided in unraveling structural features of these TFs. However, the detailed affinity and specificity by which these TFs bind to DNA sequences is still largely unknown. Qualitative methods, such as DNA footprinting, Electrophoretic Mobility Shift Assays (EMSAs), Systematic Evolution of Ligands by Exponential Enrichment (SELEX), Bacterial One Hybrid (B1H) systems, Surface Plasmon Resonance (SPR), and Protein Binding Microarrays (PBMs) have been widely used to investigate the biochemical characteristics of TF-DNA binding events. In addition to these qualitative methods, bioinformatic approaches have also assisted in TF binding site discovery. Here we discuss the advantages and limitations of these different approaches, as well as the benefits of utilizing more quantitative approaches, such as Mechanically Induced Trapping of Molecular Interactions (MITOMI), Microscale Thermophoresis (MST) and Isothermal Titration Calorimetry (ITC), in determining the biophysical basis of binding specificity of TF-DNA complexes and improving upon existing computational approaches aimed at affinity predictions.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":13477,\"status\":\"Completed\\\/Published\",\"term\":\"Spring\",\"year\":2025,\"termid\":\"2024\\\/03\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Fadwa Mekkaoui\",\"Robert  A Drewell\",\"Jacqueline  M Dresch\",\"Donald  E Spratt\"],\"sort_date\":\"2025-1-01\"},{\"activityid\":10857,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Transcription factor expression landscape in Drosophila embryonic cell lines\",\"Journal Title\":\"BMC Genomics\",\"Series Title\":null,\"Month \\\/ Season\":\"2024\",\"Year\":2024,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"25\",\"Issue Number \\\/ Edition\":\"1\",\"Page Number(s) or Number of Pages\":\"307\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":\"https:\\\/\\\/doi.org\\\/10.1186\\\/s12864-024-10241-1\",\"Description\":null,\"Include description in output citation\":0,\"Origin\":\"RIS\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":10857,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2024,\"termid\":\"2024\\\/01\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Robert A. Drewell\",\"Daniel Klonaros\",\"Jacqueline M. Dresch\"],\"sort_date\":\"2024--01\"},{\"activityid\":7646,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"&lt;strong&gt;The\\u00a0&lt;span style=&quot;font-style:italic;&quot;&gt;Dictyostelium discoideum&lt;\\\/span&gt;\\u00a0genome lacks significant DNA methylation and uncovers palindromic sequences as a source of false positives in bisulfite sequencing&lt;\\\/strong&gt;\",\"Journal Title\":\"NAR Genomics and Bioinformatics\",\"Series Title\":\"\",\"Month \\\/ Season\":\"June\",\"Year\":2023,\"Publisher\":\"\",\"Publisher City and State\":\"\",\"Publisher Country\":\"\",\"Volume\":\"\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"\",\"ISSN\":\"\",\"DOI\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":7646,\"status\":\"Completed\\\/Published\",\"term\":\"Summer\",\"year\":2023,\"termid\":\"2022\\\/05\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Robert Drewell\",\"Tayla C Cormier\",\"Jacob L Steenwyk\",\"James St. Denis\",\"Javier F Tabima Restrepo\",\"Jacqueline M. Dresch\",\"Denis A Larochelle\"],\"sort_date\":\"2023-6-01\"},{\"activityid\":7645,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"&lt;a href=&quot;https:\\\/\\\/academic.oup.com\\\/g3journal\\\/advance-article-abstract\\\/doi\\\/10.1093\\\/g3journal\\\/jkad054\\\/7068459?utm_source=advanceaccess&amp;utm_campaign=g3journal&amp;utm_medium=email&quot;&gt;Transcriptome profile in\\u00a0&lt;span style=&quot;font-style:italic;&quot;&gt;Drosophila&lt;\\\/span&gt;\\u00a0Kc and S2 embryonic cell lines&lt;\\\/a&gt;&lt;span style=&quot;font-size:16px;color:#333333;&quot;&gt;.&lt;\\\/span&gt;\",\"Journal Title\":\"G3: Genes|Genomes|Genetics\",\"Series Title\":\"\",\"Month \\\/ Season\":\"May\",\"Year\":2023,\"Publisher\":\"\",\"Publisher City and State\":\"\",\"Publisher Country\":\"\",\"Volume\":\"\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"\",\"ISSN\":\"\",\"DOI\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":7645,\"status\":\"Completed\\\/Published\",\"term\":\"May\",\"year\":2023,\"termid\":\"2022\\\/04\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Daniel Klonaros\",\"Jacqueline M. Dresch\",\"Robert Drewell\"],\"sort_date\":\"2023-5-01\"},{\"activityid\":10856,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Investigating the sequence landscape in the\\u00a0Drosophila\\u00a0initiator core promoter element using an enhanced MARZ algorithm.\\u00a0\",\"Journal Title\":\"PeerJ \",\"Series Title\":\"\",\"Month \\\/ Season\":\"\",\"Year\":2023,\"Publisher\":\"\",\"Publisher City and State\":\"\",\"Publisher Country\":\"\",\"Volume\":\"\",\"Issue Number \\\/ Edition\":\"11\",\"Page Number(s) or Number of Pages\":\"e15597\",\"ISSN\":\"\",\"DOI\":\"\",\"CoAuthor\":null,\"URL\":\"https:\\\/\\\/peerj.com\\\/articles\\\/15597\\\/\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":10856,\"status\":\"Completed\\\/Published\",\"term\":\"May\",\"year\":2023,\"termid\":\"2022\\\/04\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline M. Dresch\",\"Regan D. Conrad\",\"Daniel Klonaros\",\"Robert Drewell\"],\"sort_date\":\"2023-5-01\"},{\"activityid\":7889,\"fields\":{\"Type\":\"Presentations\",\"Title of Presentation\":\"Improving bioinformatic tools using protein-DNA binding data\",\"Conference \\\/ Meeting Name\":\"Joint Mathematics Meetings\",\"Location of Conference \\\/ Meeting\":\"Hynes Convention Center, Boston, MA\",\"Month \\\/ Season\":\"January\",\"Year\":2023,\"Sponsoring Organization\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"I gave an invited talk in the special session, &quot;The Mathematics of RNA and DNA.&quot;\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":7889,\"status\":\"Completed\\\/Published\",\"term\":\"Spring\",\"year\":2023,\"termid\":\"2022\\\/03\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline M. Dresch\"],\"sort_date\":\"2023-1-01\"},{\"activityid\":10855,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Transcriptome profile in Drosophila Kc and S2 embryonic cell lines\",\"Journal Title\":\"G3 Genes|Genomes|Genetics\",\"Series Title\":null,\"Month \\\/ Season\":\"03\",\"Year\":2023,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"13\",\"Issue Number \\\/ Edition\":\"5\",\"Page Number(s) or Number of Pages\":\"jkad054\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":null,\"Include description in output citation\":0,\"Origin\":\"BibTeX\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":10855,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2023,\"termid\":\"2023\\\/01\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Daniel Klonaros\",\"Jacqueline M Dresch\",\"Robert A Drewell\"],\"sort_date\":\"2023--01\"},{\"activityid\":1471,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"&lt;a href=&quot;https:\\\/\\\/www.sciencedirect.com\\\/science\\\/article\\\/abs\\\/pii\\\/S0025556421001292&quot;&gt;Fitting thermodynamic-based models: Incorporating parameter sensitivity improves the performance of an evolutionary algorithm&lt;\\\/a&gt;&lt;span style=&quot;font-size:16px;color:#333333;&quot;&gt;.&lt;\\\/span&gt;\",\"Journal Title\":\"Mathematical Biosciences\",\"Series Title\":\"\",\"Month \\\/ Season\":\"\",\"Year\":2021,\"Publisher\":\"\",\"Publisher City and State\":\"\",\"Publisher Country\":\"\",\"Volume\":\"\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"\",\"ISSN\":\"\",\"DOI\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1471,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2021,\"termid\":\"2021\\\/01\",\"listingorder\":6,\"completionorder\":6},{\"id\":1471,\"status\":\"Revise &amp; Resubmit\",\"term\":\"Spring\",\"year\":2020,\"termid\":\"2019\\\/03\",\"listingorder\":3,\"completionorder\":3},{\"id\":1471,\"status\":\"Revise &amp; Resubmit\",\"term\":\"Summer\",\"year\":2019,\"termid\":\"2018\\\/05\",\"listingorder\":3,\"completionorder\":3}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Michael Gaiewski\",\"Robert Drewell\",\"Jacqueline M. Dresch\"],\"sort_date\":\"2021-9-01\"},{\"activityid\":1470,\"fields\":{\"Type\":\"Papers Published - Conference Proceedings\",\"Title of Paper\":\"Biophysical and structural analysis of Antennapedia and Ultrabithorax homeodomain transcription factor-DNA binding affinities\",\"Title of Published Proceedings\":\"Protein Science\",\"Title of Conference\":\"\",\"Conference Location\":\"\",\"Month \\\/ Season\":\"\",\"Year\":2019,\"Publisher\":\"\",\"Publisher City and State\":\"\",\"Volume\":\"28\",\"Issue Number \\\/ Edition\":\"\",\"Page Numbers\":\"\",\"DOI\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1470,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2019,\"termid\":\"2019\\\/01\",\"listingorder\":6,\"completionorder\":6},{\"id\":1470,\"status\":\"Completed\\\/Published\",\"term\":\"Summer\",\"year\":2019,\"termid\":\"2018\\\/05\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jeanmarie Loss\",\"Jacqueline M. Dresch\",\"Robert Drewell\",\"Donald E. Spratt\"],\"sort_date\":\"2019-9-01\"},{\"activityid\":1647,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Analyzing the stability of gene expression using a simple reaction-diffusion model in an early Drosophila embryo\",\"Journal Title\":\"Mathematical biosciences\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2019,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"316\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"108239\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"In all complex organisms, the precise levels and timing of gene expression controls vital biological processes. In higher eukaryotes, including the fruit fly Drosophila melanogaster, the complex molecular control of transcription (the synthesis of RNA from DNA) and translation (the synthesis of proteins from RNA) events driving this gene expression are not fully understood. In particular, for Drosophila melanogaster, there is a plethora of experimental data, including quantitative measurements of both RNA and protein concentrations, but the precise mechanisms that control the dynamics of gene expression during early development and the processes which lead to steady-state levels of certain proteins remain elusive. This study analyzes a current mathematical modeling approach in an attempt to better understand the long-term behavior of gene regulation. The model is a modified reaction-diffusion equation which has been previously employed in predicting gene expression levels and studying the relative contributions of transcription and translation events to protein abundance [10,11,24]. Here, we use Matrix Algebra and Analysis techniques to study the stability of the gene expression system and analyze equilibria, using very general assumptions regarding the parameter values incorporated into the model. We prove that, given realistic biological parameter values, the system will result in a unique, stable equilibrium solution. Additionally, we give an example of this long-term behavior using the model alongside actual experimental data obtained from Drosophila embryos.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1647,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2019,\"termid\":\"2019\\\/01\",\"listingorder\":6,\"completionorder\":6},{\"id\":1647,\"status\":\"Completed\\\/Published\",\"term\":\"Summer\",\"year\":2019,\"termid\":\"2018\\\/05\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Gregory  D McCarthy\",\"Robert  A Drewell\",\"Jacqueline  M Dresch\"],\"sort_date\":\"2019-9-01\"},{\"activityid\":1656,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Rapid and efficient purification of Drosophila homeodomain transcription factors for biophysical characterization\",\"Journal Title\":\"Protein expression and purification\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2019,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"158\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"9-14\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"Homeodomain transcription factors (HD TFs) are a large class of evolutionarily conserved DNA binding proteins that contain a basic 60-amino acid region required for binding to specific DNA sites. In Drosophila melanogaster, many of these HD TFs are expressed in the early embryo and control transcription of target genes in development through their interaction with cis-regulatory modules. Previous studies where some of the Drosophila HD TFs were purified required the use of strong denaturants (i.e. 6\\u202fM urea) and multiple chromatography columns, making the downstream biochemical examination of the isolated protein difficult. To circumvent these obstacles, we have developed a streamlined expression and purification protocol to produce large yields of Drosophila HD TFs. Using the HD TFs FUSHI-TARAZU (FTZ), ANTENNAPEDIA (ANTP), ABDOMINAL-A (ABD-A), ABDOMINAL-B (ABD-B), and ULTRABITHORAX (UBX) as examples, we demonstrate that our 3-day protocol involving the overexpression of His-SUMO fusion constructs in E. coli followed by a Ni-IMAC, SUMO-tag cleavage with the SUMO protease Ulp1, and a heparin column purification produces pure, soluble protein in biological buffers around pH 7 in the absence of denaturants. Electrophoretic mobility shift assays (EMSA) confirm that the purified HD proteins are functional and nuclear magnetic resonance (NMR) spectra confirm that the purified HDs are well-folded. These purified HD TFs can be used in future biophysical experiments to structurally and biochemically characterize how and why these HD TFs bind to different DNA sequences and further probe how nucleotide differences contribute to TF-DNA specificity in the HD family.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1656,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2019,\"termid\":\"2019\\\/01\",\"listingorder\":6,\"completionorder\":6},{\"id\":1656,\"status\":\"Completed\\\/Published\",\"term\":\"Summer\",\"year\":2019,\"termid\":\"2018\\\/05\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Rachel Orlomoski\",\"Aaron Bogle\",\"Jeanmarie Loss\",\"Rylee Simons\",\"Jacqueline  M Dresch\",\"Robert  A Drewell\",\"Donald  E Spratt\"],\"sort_date\":\"2019-9-01\"},{\"activityid\":1661,\"fields\":{\"Type\":\"Presentations\",\"Title of Presentation\":\"Getting the most out of an interdisciplinary undergraduate research experience\",\"Conference \\\/ Meeting Name\":\"Gryphon and Pleiades Honors Society Seminar Series\",\"Location of Conference \\\/ Meeting\":\"Clark University\",\"Month \\\/ Season\":\"April\",\"Year\":2019,\"Sponsoring Organization\":\"Gryphon and Pleiades Honors Society\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1661,\"status\":\"Completed\\\/Published\",\"term\":\"Spring\",\"year\":2019,\"termid\":\"2018\\\/03\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline M. Dresch\"],\"sort_date\":\"2019-4-01\"},{\"activityid\":1475,\"fields\":{\"Type\":\"Presentations\",\"Title of Presentation\":\"Biophysical and structural analysis of Drosophila transcription factors\",\"Conference \\\/ Meeting Name\":\"Next-in-BIO 2018\",\"Location of Conference \\\/ Meeting\":\"Worcester MA\",\"Month \\\/ Season\":\"November\",\"Year\":2018,\"Sponsoring Organization\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1475,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2018,\"termid\":\"2018\\\/01\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Aaron Bogle\",\"Jacqueline M. Dresch\",\"Robert Drewell\",\"Donald E. Spratt\"],\"sort_date\":\"2018-11-01\"},{\"activityid\":1645,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"The folded k-spectrum kernel: A machine learning approach to detecting transcription factor binding sites with gapped nucleotide dependencies\",\"Journal Title\":\"PloS one\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2017,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"12\",\"Issue Number \\\/ Edition\":\"10\",\"Page Number(s) or Number of Pages\":\"e0185570\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"Understanding the molecular machinery involved in transcriptional regulation is central to improving our knowledge of an organism's development, disease, and evolution. The building blocks of this complex molecular machinery are an organism's genomic DNA sequence and transcription factor proteins. Despite the vast amount of sequence data now available for many model organisms, predicting where transcription factors bind, often referred to as 'motif detection' is still incredibly challenging. In this study, we develop a novel bioinformatic approach to binding site prediction. We do this by extending pre-existing SVM approaches in an unbiased way to include all possible gapped k-mers, representing different combinations of complex nucleotide dependencies within binding sites. We show the advantages of this new approach when compared to existing SVM approaches, through a rigorous set of cross-validation experiments. We also demonstrate the effectiveness of our new approach by reporting on its improved performance on a set of 127 genomic regions known to regulate gene expression along the anterio-posterior axis in early Drosophila embryos.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1645,\"status\":\"Completed\\\/Published\",\"term\":\"May\",\"year\":2017,\"termid\":\"2016\\\/04\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Abdulkadir Elmas\",\"Xiaodong Wang\",\"Jacqueline  M Dresch\"],\"sort_date\":\"2017-5-01\"},{\"activityid\":1849,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Whole genome bisulfite sequencing reveals a sparse, but robust pattern of DNA methylation in the Dictyostelium discoideum genome\",\"Journal Title\":\"BIORXIV\",\"Series Title\":\"\",\"Month \\\/ Season\":\"\",\"Year\":2017,\"Publisher\":\"\",\"Publisher City and State\":\"\",\"Publisher Country\":\"\",\"Volume\":\"\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"\",\"ISSN\":\"\",\"DOI\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1849,\"status\":\"Completed\\\/Published\",\"term\":\"Spring\",\"year\":2017,\"termid\":\"2016\\\/03\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacob Steenwyk\",\"James St. Denis\",\"Jacqueline M. Dresch\",\"Denis A Larochelle\",\"Robert Drewell\"],\"sort_date\":\"2017-1-01\"},{\"activityid\":1655,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Spatial distribution of predicted transcription factor binding sites in Drosophila ChIP peaks\",\"Journal Title\":\"Mechanisms of development\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2016,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"141\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"51-61\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"In the development of the Drosophila embryo, gene expression is directed by the sequence-specific interactions of a large network of protein transcription factors (TFs) and DNA cis-regulatory binding sites. Once the identity of the typically 8-10bp binding sites for any given TF has been determined by one of several experimental procedures, the sequences can be represented in a position weight matrix (PWM) and used to predict the location of additional TF binding sites elsewhere in the genome. Often, alignments of large (&gt;200bp) genomic fragments that have been experimentally determined to bind the TF of interest in Chromatin Immunoprecipitation (ChIP) studies are trimmed under the assumption that the majority of the binding sites are located near the center of all the aligned fragments. In this study, ChIP\\\/chip datasets are analyzed using the corresponding PWMs for the well-studied TFs; CAUDAL, HUNCHBACK, KNIRPS and KRUPPEL, to determine the distribution of predicted binding sites. All four TFs are critical regulators of gene expression along the anterio-posterior axis in early Drosophila development. For all four TFs, the ChIP peaks contain multiple binding sites that are broadly distributed across the genomic region represented by the peak, regardless of the prediction stringency criteria used. This result suggests that ChIP peak trimming may exclude functional binding sites from subsequent analyses.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1655,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2016,\"termid\":\"2016\\\/01\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Kade  P Pettie\",\"Jacqueline  M Dresch\",\"Robert  A Drewell\"],\"sort_date\":\"2016-9-01\"},{\"activityid\":1659,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Quantitative perturbation-based analysis of gene expression predicts enhancer activity in early Drosophila embryo\",\"Journal Title\":\"eLife\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2016,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"5\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"Enhancers constitute one of the major components of regulatory machinery of metazoans. Although several genome-wide studies have focused on finding and locating enhancers in the genomes, the fundamental principles governing their internal architecture and cis-regulatory grammar remain elusive. Here, we describe an extensive, quantitative perturbation analysis targeting the dorsal-ventral patterning gene regulatory network (GRN) controlled by Drosophila NF-\\u03baB homolog Dorsal. To understand transcription factor interactions on enhancers, we employed an ensemble of mathematical models, testing effects of cooperativity, repression, and factor potency. Models trained on the dataset correctly predict activity of evolutionarily divergent regulatory regions, providing insights into spatial relationships between repressor and activator binding sites. Importantly, the collective predictions of sets of models were effective at novel enhancer identification and characterization. Our study demonstrates how experimental dataset and modeling can be effectively combined to provide quantitative insights into cis-regulatory information on a genome-wide scale.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1659,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2016,\"termid\":\"2016\\\/01\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Rupinder Sayal\",\"Jacqueline  M Dresch\",\"Irina Pushel\",\"Benjamin  R Taylor\",\"David  N Arnosti\"],\"sort_date\":\"2016-9-01\"},{\"activityid\":1652,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Nucleotide Interdependency in Transcription Factor Binding Sites in the Drosophila Genome\",\"Journal Title\":\"Gene regulation and systems biology\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2016,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"10\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"21-33\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"A long-standing objective in modern biology is to characterize the molecular components that drive the development of an organism. At the heart of eukaryotic development lies gene regulation. On the molecular level, much of the research in this field has focused on the binding of transcription factors (TFs) to regulatory regions in the genome known as cis-regulatory modules (CRMs). However, relatively little is known about the sequence-specific binding preferences of many TFs, especially with respect to the possible interdependencies between the nucleotides that make up binding sites. A particular limitation of many existing algorithms that aim to predict binding site sequences is that they do not allow for dependencies between nonadjacent nucleotides. In this study, we use a recently developed computational algorithm, MARZ, to compare binding site sequences using 32 distinct models in a systematic and unbiased approach to explore nucleotide dependencies within binding sites for 15 distinct TFs known to be critical to Drosophila development. Our results indicate that many of these proteins have varying levels of nucleotide interdependencies within their DNA recognition sequences, and that, in some cases, models that account for these dependencies greatly outperform traditional models that are used to predict binding sites. We also directly compare the ability of different models to identify the known KRUPPEL TF binding sites in CRMs and demonstrate that a more complex model that accounts for nucleotide interdependencies performs better when compared with simple models. This ability to identify TFs with critical nucleotide interdependencies in their binding sites will lead to a deeper understanding of how these molecular characteristics contribute to the architecture of CRMs and the precise regulation of transcription during organismal development. \",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1652,\"status\":\"Completed\\\/Published\",\"term\":\"May\",\"year\":2016,\"termid\":\"2015\\\/04\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline  M Dresch\",\"Rowan  G Zellers\",\"Daniel  K Bork\",\"Robert  A Drewell\"],\"sort_date\":\"2016-5-01\"},{\"activityid\":1649,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"The Wisdom of Crowds: Can Mathematical Models Crack the cis Regulatory Code?\",\"Journal Title\":\"Cell systems\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2015,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"1\",\"Issue Number \\\/ Edition\":\"6\",\"Page Number(s) or Number of Pages\":\"379-80\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"Genomic information includes not just a &quot;parts list&quot; of encoded proteins and RNAs, but also the information on regulation and function. To understand this more complex, deeper layer of biological information, recent efforts have turned to mathematical models as discovery engines of the cis regulatory code. \",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1649,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2015,\"termid\":\"2015\\\/01\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline  M Dresch\",\"David  N Arnosti\"],\"sort_date\":\"2015-9-01\"},{\"activityid\":1648,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Global sensitivity analysis of a dynamic model for gene expression in Drosophila embryos\",\"Journal Title\":\"PeerJ\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2015,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"3\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"e1022\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"It is well known that gene regulation is a tightly controlled process in early organismal development. However, the roles of key processes involved in this regulation, such as transcription and translation, are less well understood, and mathematical modeling approaches in this field are still in their infancy. In recent studies, biologists have taken precise measurements of protein and mRNA abundance to determine the relative contributions of key factors involved in regulating protein levels in mammalian cells. We now approach this question from a mathematical modeling perspective. In this study, we use a simple dynamic mathematical model that incorporates terms representing transcription, translation, mRNA and protein decay, and diffusion in an early Drosophila embryo. We perform global sensitivity analyses on this model using various different initial conditions and spatial and temporal outputs. Our results indicate that transcription and translation are often the key parameters to determine protein abundance. This observation is in close agreement with the experimental results from mammalian cells for various initial conditions at particular time points, suggesting that a simple dynamic model can capture the qualitative behavior of a gene. Additionally, we find that parameter sensitivites are temporally dynamic, illustrating the importance of conducting a thorough global sensitivity analysis across multiple time points when analyzing mathematical models of gene regulation. \",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1648,\"status\":\"Completed\\\/Published\",\"term\":\"May\",\"year\":2015,\"termid\":\"2014\\\/04\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Gregory  D McCarthy\",\"Robert  A Drewell\",\"Jacqueline  M Dresch\"],\"sort_date\":\"2015-5-01\"},{\"activityid\":1658,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"MARZ: an algorithm to combinatorially analyze gapped n-mer models of transcription factor binding\",\"Journal Title\":\"BMC bioinformatics\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2015,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"16\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"30\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"A key challenge in understanding the molecular mechanisms that control gene regulation is the characterization of the specificity with which transcription factor proteins bind to specific DNA sequences. A number of computational approaches have been developed to examine these interactions, including simple mononucleotide and dinucleotide position weight matrix models.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1658,\"status\":\"Completed\\\/Published\",\"term\":\"Intersession\",\"year\":2015,\"termid\":\"2014\\\/02\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Rowan  G Zellers\",\"Robert  A Drewell\",\"Jacqueline  M Dresch\"],\"sort_date\":\"2015-1-01\"},{\"activityid\":1657,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Deciphering the combinatorial architecture of a  Drosophila homeotic gene enhancer\",\"Journal Title\":\"Mechanisms of development\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2014,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"131\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"68-77\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"In Drosophila, the 330 kb bithorax complex regulates cellular differentiation along the anterior\\u2013posterior axis during development in the thorax and abdomen and is comprised of three homeotic genes: Ultrabithorax, abdominal-A, and Abdominal-B. The expression of each of these genes is in turn controlled through interactions between transcription factors and a number of cis-regulatory modules in the neighboring intergenic regions. In this study, we examine how the sequence architecture of transcription factor binding sites mediates the functional activity of one of these cis-regulatory modules. Using computational, mathematical modeling and experimental molecular genetic approaches we investigate the IAB7b enhancer, which regulates Abdominal-B expression specifically in the presumptive seventh and ninth abdominal segments of the early embryo. A cross-species comparison of the IAB7b enhancer reveals an evolutionarily conserved signature motif containing two FUSHI-TARAZU activator transcription factor binding sites. We find that the transcriptional repressors KNIRPS, KRUPPEL and GIANT are able to restrict reporter gene expression to the posterior abdominal segments, using different molecular mechanisms including short-range repression and competitive binding. Additionally, we show the functional importance of the spacing between the two FUSHI-TARAZU binding sites and discuss the potential importance of cooperativity for transcriptional activation. Our results demonstrate that the transcriptional output of the IAB7b cis-regulatory module relies on a complex set of combinatorial inputs mediated by specific transcription factor binding and that the sequence architecture at this enhancer is critical to maintain robust regulatory function.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1657,\"status\":\"Completed\\\/Published\",\"term\":\"Spring\",\"year\":2014,\"termid\":\"2013\\\/03\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Robert  A Drewell\",\"Michael  J Nevarez\",\"Je S Kurata\",\"Laure N Winkler\",\"Lily Li\",\"Jacqueline  M Dresch\"],\"sort_date\":\"2014-1-01\"},{\"activityid\":1650,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"A primer on thermodynamic-based models for deciphering transcriptional regulatory logic\",\"Journal Title\":\"Biochimica et biophysica acta\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2013,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"1829\",\"Issue Number \\\/ Edition\":\"9\",\"Page Number(s) or Number of Pages\":\"946-53\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"A rigorous analysis of transcriptional regulation at the DNA level is crucial to the understanding of many biological systems. Mathematical modeling has offered researchers a new approach to understanding this central process. In particular, thermodynamic-based modeling represents the most biophysically informed approach aimed at connecting DNA level regulatory sequences to the expression of specific genes. The goal of this review is to give biologists a thorough description of the steps involved in building, analyzing, and implementing a thermodynamic-based model of transcriptional regulation. The data requirements for this modeling approach are described, the derivation for a specific regulatory region is shown, and the challenges and future directions for the quantitative modeling of gene regulation are discussed. \",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1650,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2013,\"termid\":\"2013\\\/01\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline  M Dresch\",\"Megan Richards\",\"Ahmet Ay\"],\"sort_date\":\"2013-9-01\"},{\"activityid\":1654,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Flanking sequence context-dependent transcription factor binding in early Drosophila development\",\"Journal Title\":\"BMC bioinformatics\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2013,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"14\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"298\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"Gene expression in the Drosophila embryo is controlled by functional interactions between a large network of protein transcription factors (TFs) and specific sequences in DNA cis-regulatory modules (CRMs). The binding site sequences for any TF can be experimentally determined and represented in a position weight matrix (PWM). PWMs can then be used to predict the location of TF binding sites in other regions of the genome, although there are limitations to this approach as currently implemented.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1654,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2013,\"termid\":\"2013\\\/01\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jessica  L Stringham\",\"Adam  S Brown\",\"Robert  A Drewell\",\"Jacqueline  M Dresch\"],\"sort_date\":\"2013-9-01\"},{\"activityid\":1651,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"TWO-LAYER MATHEMATICAL MODELING OF GENE EXPRESSION: INCORPORATING DNA-LEVEL INFORMATION AND SYSTEM DYNAMICS\",\"Journal Title\":\"SIAM journal on applied mathematics\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2013,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"73\",\"Issue Number \\\/ Edition\":\"2\",\"Page Number(s) or Number of Pages\":\"804-826\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"High-throughput genome sequencing and transcriptome analysis have provided researchers with a quantitative basis for detailed modeling of gene expression using a wide variety of mathematical models. Two of the most commonly employed approaches used to model eukaryotic gene regulation are systems of differential equations, which describe time-dependent interactions of gene networks, and thermodynamic equilibrium approaches that can explore DNA-level transcriptional regulation. To combine the strengths of these approaches, we have constructed a new two-layer mathematical model that provides a dynamical description of gene regulatory systems, using detailed DNA-based information, as well as spatial and temporal transcription factor concentration data. We also developed a semi-implicit numerical algorithm for solving the model equations and demonstrate here the efficiency of this algorithm through stability and convergence analyses. To test the model, we used it together with the semi-implicit algorithm to simulate a  gene regulatory circuit that drives development in the dorsal-ventral axis of the blastoderm-stage embryo, involving three genes. For model validation, we have done both mathematical and statistical comparisons between the experimental data and the model's simulated data. Where protein and -regulatory information is available, our two-layer model provides a method for recapitulating and predicting dynamic aspects of eukaryotic transcriptional systems that will greatly improve our understanding of gene regulation at a global level.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1651,\"status\":\"Completed\\\/Published\",\"term\":\"Spring\",\"year\":2013,\"termid\":\"2012\\\/03\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline  M Dresch\",\"M A Thompson\",\"David  N Arnosti\",\"Chichia Chiu\"],\"sort_date\":\"2013-1-01\"},{\"activityid\":1660,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Global parameter estimation for thermodynamic models of transcriptional regulation\",\"Journal Title\":\"Methods (San Diego, Calif.)\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2013,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"62\",\"Issue Number \\\/ Edition\":\"1\",\"Page Number(s) or Number of Pages\":\"99-108\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"Deciphering the mechanisms involved in gene regulation holds the key to understanding the control of central biological processes, including human disease, population variation, and the evolution of morphological innovations. New experimental techniques including whole genome sequencing and transcriptome analysis have enabled comprehensive modeling approaches to study gene regulation. In many cases, it is useful to be able to assign biological significance to the inferred model parameters, but such interpretation should take into account features that affect these parameters, including model construction and sensitivity, the type of fitness calculation, and the effectiveness of parameter estimation. This last point is often neglected, as estimation methods are often selected for historical reasons or for computational ease. Here, we compare the performance of two parameter estimation techniques broadly representative of local and global approaches, namely, a quasi-Newton\\\/Nelder-Mead simplex (QN\\\/NMS) method and a covariance matrix adaptation-evolutionary strategy (CMA-ES) method. The estimation methods were applied to a set of thermodynamic models of gene transcription applied to regulatory elements active in the Drosophila embryo. Measuring overall fit, the global CMA-ES method performed significantly better than the local QN\\\/NMS method on high quality data sets, but this difference was negligible on lower quality data sets with increased noise or on data sets simplified by stringent thresholding. Our results suggest that the choice of parameter estimation technique for evaluation of gene expression models depends both on quality of data, the nature of the models [again, remains to be established] and the aims of the modeling effort. \",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1660,\"status\":\"Completed\\\/Published\",\"term\":\"Summer\",\"year\":2013,\"termid\":\"2012\\\/05\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Yerzhan Suleimenov\",\"Ahmet Ay\",\"Md  A Samee\",\"Jacqueline  M Dresch\",\"Saurabh Sinha\",\"David  N Arnosti\"],\"sort_date\":\"2013-1-01\"},{\"activityid\":1653,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects\",\"Journal Title\":\"BMC systems biology\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2010,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"4\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"142\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"Quantitative models of gene expression generate parameter values that can shed light on biological features such as transcription factor activity, cooperativity, and local effects of repressors. An important element in such investigations is sensitivity analysis, which determines how strongly a model's output reacts to variations in parameter values. Parameters of low sensitivity may not be accurately estimated, leading to unwarranted conclusions. Low sensitivity may reflect the nature of the biological data, or it may be a result of the model structure. Here, we focus on the analysis of thermodynamic models, which have been used extensively to analyze gene transcription. Extracted parameter values have been interpreted biologically, but until now little attention has been given to parameter sensitivity in this context.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1653,\"status\":\"Completed\\\/Published\",\"term\":\"Fall\",\"year\":2010,\"termid\":\"2010\\\/01\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline  M Dresch\",\"Xiaozhou Liu\",\"David  N Arnosti\",\"Ahmet Ay\"],\"sort_date\":\"2010-9-01\"},{\"activityid\":1646,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"Network structure, and vaccination strategy and effort interact to affect the dynamics of influenza epidemics\",\"Journal Title\":\"Journal of theoretical biology\",\"Series Title\":null,\"Month \\\/ Season\":null,\"Year\":2007,\"Publisher\":null,\"Publisher City and State\":null,\"Publisher Country\":null,\"Volume\":\"246\",\"Issue Number \\\/ Edition\":\"2\",\"Page Number(s) or Number of Pages\":\"205-13\",\"ISSN\":null,\"DOI\":null,\"CoAuthor\":null,\"URL\":null,\"Description\":\"There is growing interest in understanding and controlling the spread of diseases through realistically structured host populations. We investigate how network structures, ranging from circulant, through small-world networks, to random networks, and vaccination strategy and effort interact to influence the proportion of the population infected, the size and timing of the epidemic peak, and the duration of the epidemic. We found these three factors, and their higher-order interactions, significantly influenced epidemic development and extent. Increasing vaccination effort (from 0% to 90%) decreased the number of hosts infected while increasing network randomness worked to increase disease spread. On average, vaccinating hosts based on degree (hubs) resulted in the smallest epidemics while vaccinating hosts with the highest clustering coefficient resulted in the largest epidemics. In a targeted test of five vaccination strategies on a small-world network (probability of rewiring edges=5%) with 10% vaccination effort we found that vaccinating hosts preferentially with high-clustering coefficients (similar to real-world strategies) resulted in twice the number of hosts infected as random vaccinations and nearly a 30-fold higher number of cases than our strategy targeting hubs (highest degree hosts). Our model suggests how vaccinations might be implemented to minimize the extent of an epidemic (e.g., duration and total number infected) as well as the timing and number of hosts infected at a given time over a wide range of structured host networks.\",\"Include description in output citation\":0,\"Origin\":\"PubMed\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":1646,\"status\":\"Completed\\\/Published\",\"term\":\"May\",\"year\":2007,\"termid\":\"2006\\\/04\",\"listingorder\":6,\"completionorder\":6}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"G Hartvigsen\",\"J  M Dresch\",\"A  L Zielinski\",\"A  J Macula\",\"C C C Leary\"],\"sort_date\":\"2007-5-01\"},{\"activityid\":13470,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"&lt;p&gt;&lt;b&gt;&lt;span&gt;Biophysical DNA binding activities of the EVEN-SKIPPED and FUSHI-TARAZU homeodomain transcription factors&lt;\\\/span&gt;&lt;\\\/b&gt;&lt;span&gt;&lt;\\\/span&gt;&lt;\\\/p&gt;\",\"Journal Title\":\"Plos Genetics\",\"Series Title\":\"\",\"Month \\\/ Season\":\"\",\"Year\":null,\"Publisher\":\"\",\"Publisher City and State\":\"\",\"Publisher Country\":\"\",\"Volume\":\"\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"\",\"ISSN\":\"\",\"DOI\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":13470,\"status\":\"In Progress\",\"term\":\"Spring\",\"year\":2025,\"termid\":\"2024\\\/03\",\"listingorder\":1,\"completionorder\":1},{\"id\":13470,\"status\":\"In Progress\",\"term\":\"Summer\",\"year\":2024,\"termid\":\"2023\\\/05\",\"listingorder\":1,\"completionorder\":1}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Jacqueline M. Dresch\",\"Fadwa Mekkaoui\",\"Don E. Spratt\",\"Robert Drewell\"],\"sort_date\":\"2000-01-01\"},{\"activityid\":13471,\"fields\":{\"Type\":\"Articles in Refereed Journals\",\"Title\":\"&lt;p&gt;&lt;b&gt;&lt;span&gt;Identification of novel components of the retinal determination gene network in Drosophila cell lines&lt;\\\/span&gt;&lt;\\\/b&gt;&lt;span&gt;&lt;\\\/span&gt;&lt;\\\/p&gt;\",\"Journal Title\":\"Open Biology\",\"Series Title\":\"\",\"Month \\\/ Season\":\"\",\"Year\":null,\"Publisher\":\"\",\"Publisher City and State\":\"\",\"Publisher Country\":\"\",\"Volume\":\"\",\"Issue Number \\\/ Edition\":\"\",\"Page Number(s) or Number of Pages\":\"\",\"ISSN\":\"\",\"DOI\":\"\",\"CoAuthor\":null,\"URL\":\"\",\"Description\":\"\",\"Include description in output citation\":0,\"Origin\":\"Manual\"},\"facultyid\":\"C70231168\",\"status\":[{\"id\":13471,\"status\":\"Revise &amp; Resubmit\",\"term\":\"Spring\",\"year\":2025,\"termid\":\"2024\\\/03\",\"listingorder\":3,\"completionorder\":3},{\"id\":13471,\"status\":\"Revise &amp; Resubmit\",\"term\":\"Summer\",\"year\":2024,\"termid\":\"2023\\\/05\",\"listingorder\":3,\"completionorder\":3}],\"userid\":\"C70231168\",\"attachments\":[],\"coauthors_list\":[\"Robert Drewell\",\"Jacqueline M. 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the nature of TF-DNA interactions through biophysical measurements, bioinformatics, and synthetic biology\",\"Sponsor\":\"Faculty Development Funds (Larry Fechter and Thomas Macke Stansbury)\",\"Grant ID \\\/ Contract ID\":\"\",\"Award Date\":\"2020-02-26\",\"Start Date\":\"2020-06-01\",\"End Date\":\"2021-05-31\",\"Period Length\":1,\"Period Unit\":\"Year\",\"Indirect Funding\":0,\"Indirect Cost Rate\":null,\"Total Funding\":\"7500\",\"Total Direct Funding\":null,\"Currency Type\":\"USD\",\"Description\":\"\",\"Abstract\":\"&lt;p&gt;Over the past two years, a very fruitful and exciting interdisciplinary collaboration has blossomed between our three research groups at Clark University: the Spratt lab in the Chemistry Department, the Drewell lab in the Biology Department, and the Dresch group in Mathematics and Computer Science. 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