[cid:992ce85c-f893-44db-9c7e-3d3e9a845761] Dear EMBRIO Members: All-Hands Lab Meeting this afternoon at 3pm ET Plan to join our All-Hands Lab Meeting this afternoon at 3pm ET, featuring research led by Razeen Shaikh and Greg Reeves (Reeves Lab, Texas A&M) presenting "MIDOE: Maximally-informed Design of Experiment to infer experimentally inaccessible transcription factors dynamics". Abstract: The TGF-β/Smad signaling pathway regulates growth, development, and homeostasis of tissues across the animal kingdom. The pathway is activated when transforming growth factor -β (TGF-β) binds to its cognate transmembrane receptors to activate Smad2 by phosphorylation. The activated phosphor-Smad2 (PSmad2) undergoes a series of biochemical interactions with transcriptional activator Smad4 to form several oligomers, including the transcription factor (PSmad2)2/Smad4, which regulates target gene expression. Quantitative live cell imaging and mathematical modeling have been used to estimate the dynamics of (PSmad2)2/Smad4. However, due to the emergent nature of Smad2-Smad4 interactions, deconvolving the dynamics of the (PSmad2)2/Smad4 is challenging. We show that the Smad model is sloppy, has large parameter uncertainties (Ο∼1015), and the eigenvalues of the Fisher Information Matrix span over several decades. As such, well-fit parameter sets generate highly under-constrained predictions. To overcome this, we employ Profile Log-Likelihood to guide maximally informed design of experiments (MIDOE) and infer the dynamics of (PSmad2)2/Smad4. We generate these experiments computationally and validate that MIDOE can optimally constrain model predictions. We demonstrate that such careful analysis would not only improve the predictive power of models in systems biology but also reduce the time and expense of performing non-optimal experiments. Zoom link: https://purdue-edu.zoom.us/j/92061591849?pwd=wclgpzLpzWKsZ9M2XYwM7Kbumaabr3.1&from=addon<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpurdue-edu.zoom.us%2Fj%2F92061591849%3Fpwd%3DwclgpzLpzWKsZ9M2XYwM7Kbumaabr3.1%26from%3Daddon&data=05%7C02%7Cembrio-list%40ecn.purdue.edu%7C22e9425a96374efb3cd108de04f1e75a%7C4130bd397c53419cb1e58758d6d63f21%7C1%7C0%7C638953634185837974%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=1fB6PMAft4LgiPx9HNx76nB%2F0XW8WBqpxsXma%2F4u75g%3D&reserved=0> To access the introductory sessions on Biological Modeling Workflow from our first two all-hands lab meetings, see the slides and materials from Hayden Fennel and the Glazier lab via our shared box account under "All-Hands Meeting Recordings > 2025 ": https://app.box.com/s/vmoaq3w216ye0c78vxhyzmhh0j4vr8mx<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fapp.box.com%2Fs%2Fvmoaq3w216ye0c78vxhyzmhh0j4vr8mx&data=05%7C02%7Cembrio-list%40ecn.purdue.edu%7C22e9425a96374efb3cd108de04f1e75a%7C4130bd397c53419cb1e58758d6d63f21%7C1%7C0%7C638953634185849267%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=4gRfpzyFWqP%2Bv7kD5jobKvvtIa%2Ba0aFFk6uTannZbEA%3D&reserved=0> Light-Sheet Fluorescence Microscopy Workshop: Advanced 3D Imaging for Biological Research Led by Purdue Bindley Bioscience Center (with Dr. Weiwei Zhang), together with Bruker and EMBRIO Institute. This is an excellent opportunity for EMBRIO members to learn and gain skills in this imaging modality. The workshop will be held October 28-29, 2025, on the Purdue campus, with options for the first half of day one via Zoom. For EMBRIO members at our partner locations interested in attending this training, please contact Brent regarding travel (laddb@purdue.edu). For questions about the workshop please contact Weiwei (zhan2190@purdue.edu ) See the attached flyer and registration page for details. Registration is free: https://purdue.ca1.qualtrics.com/jfe/form/SV_1GrEoUEHdatNBFY<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpurdue.ca1.qualtrics.com%2Fjfe%2Fform%2FSV_1GrEoUEHdatNBFY&data=05%7C02%7Cembrio-list%40ecn.purdue.edu%7C22e9425a96374efb3cd108de04f1e75a%7C4130bd397c53419cb1e58758d6d63f21%7C1%7C0%7C638953634185858597%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=ME2KHpCHl8U0jvwRYXVYDPijSZRb6NpaeCL7bOAefGw%3D&reserved=0> The 150th Karling Lecture at Purdue University's Department of Biological Sciences will be given by Dr. Denise Montell on October 7, 2025 Dear EMBRIO investigators, I am hosting Dr. Denise Montell, a world-renowned cell biologist, in the fall. She will deliver our department's Karling Lecture on Oct 7, 12:30-1:30 pm in DLR 131. I have attached her Wikipedia page FYI: https://en.wikipedia.org/wiki/Denise_Montell<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FDenise_Montell&data=05%7C02%7Cembrio-list%40ecn.purdue.edu%7C22e9425a96374efb3cd108de04f1e75a%7C4130bd397c53419cb1e58758d6d63f21%7C1%7C0%7C638953634185867385%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=1104ESpxZVK4ZgPpJ57222fR3tv0Ru6kyUJYlcKICEQ%3D&reserved=0> Best, Qing qingdeng@purdue.edu https://www.denglab.us<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.denglab.us%2F&data=05%7C02%7Cembrio-list%40ecn.purdue.edu%7C22e9425a96374efb3cd108de04f1e75a%7C4130bd397c53419cb1e58758d6d63f21%7C1%7C0%7C638953634185876026%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=ltOSztHHR7dR63RQzVV3nQTAIfdEag5Nz8ctJ2%2B4l4o%3D&reserved=0> Faculty and Research Staff: Leveraging EMBRIO in Future Proposals The beginnings of coordinating proposal efforts that dovetail with EMBRIO and member collaboration - see the editable Google spreadsheet to view potential opportunities and add new. Currently working on a strategy to best position and support these efforts among the membership. https://docs.google.com/spreadsheets/d/1MzX5ZAyn5LjiEX5uKUm1RNz8W8URxU62/edit?usp=sharing&ouid=107962836095749734864&rtpof=true&sd=true<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fdocs.google.com%2Fspreadsheets%2Fd%2F1MzX5ZAyn5LjiEX5uKUm1RNz8W8URxU62%2Fedit%3Fusp%3Dsharing%26ouid%3D107962836095749734864%26rtpof%3Dtrue%26sd%3Dtrue&data=05%7C02%7Cembrio-list%40ecn.purdue.edu%7C22e9425a96374efb3cd108de04f1e75a%7C4130bd397c53419cb1e58758d6d63f21%7C1%7C0%7C638953634185886779%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=Nl13FZyx9MPpnB%2B6WDtUa56mPM8ZZaK7wRfIwXgRKak%3D&reserved=0> Brent T. Ladd, Senior Research Program Manager, EMBRIO Institute<https://www.purdue.edu/research/embrio/> Weldon School of Biomedical Engineering, Purdue University Office: Hall for Discovery Learning and Research, Ste. 203 207 S. Martin Jischke Drive West Lafayette, IN 47907 laddb@purdue.edu