Uploaded May 2026 | Updated September 2026, 3 weeks ago
Recorded 20 May 2026. Brian Spears of Lawrence Livermore National Laboratory presents "The Genesis Mission: AI for US Science and Security Transformation" at IPAM's Multi-Fidelity Methods to Enable Robust Optimization and Real-Time Control of Fusion Processes Workshop.
Abstract: Genesis Mission is a Department of Energy AI effort aimed at recruiting cutting-edge AI for science in order to double US R&D productivity while delivering innovation overmatch: the ability to mitigate emerging threats on timescales faster than those of U.S. adversaries. The effort is organized around two coupled thrusts. The first is a set of Science and Technology Challenges that define high-value problems across science, national security, and applied energy, thereby providing the mission pull for development. The second is the Genesis Platform, a federated, agent-first platform that connects frontier AI models, trusted data, high-performance computing, laboratory facilities, and mission workflows through governed and reusable interfaces.
This talk will describe the top-level goals and architecture of Genesis and explain how the Platform is intended to transform isolated demonstrations into durable operational capability. I will present examples and demonstrations spanning national security, applied energy, and scientific discovery to illustrate how AI-enabled workflows can support planning, analysis, orchestration, and decision-making across heterogeneous computational and experimental environments.
I will also discuss why Genesis is relevant to the applied mathematics community. Core technical challenges include modeling and simulation, inverse problems, optimization and control, uncertainty quantification, scientific machine learning, surrogate modeling, verification and validation, and reliable autonomous workflow execution. These areas place applied mathematics at the center of both the scientific opportunity and the rigor required for mission deployment. The talk will conclude with a call for engagement from the applied mathematics community in methods, benchmarks, evaluation, and co-design.
Learn more online at: https://www.ipam.ucla.edu/programs/workshops/workshop-iv-multi-fidelity-methods-to-enable-robust-optimization-and-real-time-control-of-fusion-processes/?tab=overview
Recorded 20 May 2026. Brian Spears of Lawrence Livermore National Laboratory presents "The Genesis Mission: AI for US Science and Security Transformation" at IPAM's Multi-Fidelity Methods to Enable Robust Optimization and Real-Time Control of Fusion Processes Workshop.
Abstract: Genesis Mission is a Department of Energy AI effort aimed at recruiting cutting-edge AI for science in order to double US R&D productivity while delivering innovation overmatch: the ability to mitigate emerging threats on timescales faster than those of U.S. adversaries. The effort is organized around two coupled thrusts. The first is a set of Science and Technology Challenges that define high-value problems across science, national security, and applied energy, thereby providing the mission pull for development. The second is the Genesis Platform, a federated, agent-first platform that connects frontier AI models, trusted data, high-performance computing, laboratory facilities, and mission workflows through governed and reusable interfaces.
This talk will describe the top-level goals and architecture of Genesis and explain how the Platform is intended to transform isolated demonstrations into durable operational capability. I will present examples and demonstrations spanning national security, applied energy, and scientific discovery to illustrate how AI-enabled workflows can support planning, analysis, orchestration, and decision-making across heterogeneous computational and experimental environments.
I will also discuss why Genesis is relevant to the applied mathematics community. Core technical challenges include modeling and simulation, inverse problems, optimization and control, uncertainty quantification, scientific machine learning, surrogate modeling, verification and validation, and reliable autonomous workflow execution. These areas place applied mathematics at the center of both the scientific opportunity and the rigor required for mission deployment. The talk will conclude with a call for engagement from the applied mathematics community in methods, benchmarks, evaluation, and co-design.
Learn more online at: https://www.ipam.ucla.edu/programs/workshops/workshop-iv-multi-fidelity-methods-to-enable-robust-optimization-and-real-time-control-of-fusion-processes/?tab=overview

![Eduardo Sontag - A Mathematical Model of Evolution of Drug-Induced Resistance - IPAM at UCLA
Recorded 23 February 2026. Eduardo Sontag of Northeastern University presents A Mathematical Model of Evolution of Drug-Induced Resistance at IPAMs Mathematics of Cancer: Open Mathematical Problems Workshop.
Abstract: Resistance to chemotherapy is a major impediment to the successful treatment of cancer. Classically, resistance has been thought to arise primarily through random genetic mutations, after which mutated cells expand via Darwinian selection. However, recent experimental evidence suggests that the progression to resistance need not occur randomly, but instead may be induced by the therapeutic agent itself. This process of resistance induction can be a result of genetic changes, or can occur through epigenetic alterations that cause otherwise drug-sensitive cancer cells to undergo phenotype switching. This relatively novel notion of resistance further complicates the already challenging task of designing treatment protocols that minimize the risk of evolving resistance.
In an effort to better understand treatment resistance, we developed in [1] a mathematical modeling framework that incorporates both spontaneous and drug-induced resistance. Our model demonstrates that the ability (or lack thereof) of a drug to induce resistance can result in qualitatively different responses to the same drug dose and delivery schedule. The importance of induced resistance in treatment response led us to ask if, in our model, one can determine the resistance induction rate of a drug for a given treatment protocol, and this led to a structural identifiability theorem. In [2], we worked out an optimal control problem related to the model in [1]. The control structure is precisely characterized as a concatenation of bang-bang and path-constrained arcs via the Pontryagin Maximum Principle and differential Lie algebraic techniques. A structural identifiability analysis is also presented, demonstrating that patient-specific parameters may be measured and thus utilized in the design of optimal therapies prior to the commencement of therapy.
In the recent paper [3], and for a slight modification of the model in [2] and were able to obtains excellent fits to time-resolved in-vitro experimental data. From observational data of total numbers of cells, the model unravels the relative proportions of sensitive and resistance subpopulations, and quantifies their dynamics as a function of drug dose. The predictions are then validated on data on drug doses which were not used when fitting parameters. The model is then used, in conjunction with optimal control techniques, in order to discover dosing strategies that might lead to better outcomes as quantified by lower total cell volume.
This is joint work with Jana Gevertz, Jim Green, Samantha Propsperi, Cynthia Sanchez Tapia, and Natacha Comandante-Lou
References:
[1] J.M. Greene, J.L. Gevertz, and E. D. Sontag. A mathematical approach to distinguish spontaneous from induced evolution of drug resistance during cancer treatment. JCO Clinical Cancer Informatics, 2019.
[2] J. M. Greene, C. Sanchez-Tapia, and E.D. Sontag. Mathematical details on a cancer resistance model. Frontiers in Bioengineering and Biotechnology, 2020.
[3] J.L. Gevertz, J.M. Greene, Samantha Propsperi, Natacha Comandante-Lou, and E. D. Sontag. Understanding therapeutic tolerance through a mathematical model of drug-induced resistance, npj Systems Biology and Applications, 2025.
Learn more online at: https://www.ipam.ucla.edu/programs/workshops/mathematics-of-cancer-open-mathematical-problems/ Eduardo Sontag - A Mathematical Model of Evolution of Drug-Induced Resistance - IPAM at UCLA](https://i.ytimg.com/vi/lkbP_2zM4bA/mqdefault.jpg)








