Uploaded June 2025 | Updated September 2026, 2 weeks ago
Models, Inference and Algorithms
March 11, 2025
Broad Institute of MIT and Harvard
Primer: Heterogeneous reconstruction in cryo-EM
Rishwanth Raghu
Princeton University Department of Computer Science
Meeting: Machine learning for visualizing structural landscapes inside the cell
Ellen Zhong
Princeton University
Structural biology has been transformed by breakthroughs in deep learning methods for protein structure prediction. In parallel, advances in cryo-electron microscopy and tomography have produced new opportunities to study the dynamics and interactions of biomolecular complexes. In this seminar, I will describe the algorithmic challenges at the frontier of structure determination via cryo-EM. I will overview cryoDRGN, a machine learning system for heterogeneous cryo-EM and cryo-ET reconstruction. Along the way, I will overview recent progress in our group on reconstructing complex mixtures, developing a challenging benchmark for structural heterogeneity, and visualizing dynamic biomolecular complexes in situ.
Bio: Ellen Zhong is an Assistant Professor of Computer Science at Princeton University where she is also affiliated with the Princeton Laboratory for Artificial Intelligence, the Center for Statistics and Machine Learning, and the Omenn-Darling Bioengineering Institute. Her group’s research spans methodological research in AI and computer vision, as well as close collaboration with experimentalists in molecular and structural biology. Previously, she has worked on the AlphaFold team at Google DeepMind and at D. E. Shaw Research on molecular dynamics for drug discovery. She obtained her B.S. from the University of Virginia in 2014 and her Ph.D. from MIT in 2022 before joining the Princeton faculty.
For more information visit: broadinstitute.org/talks/spring-2025/mia
Copyright Broad Institute, 2024. All rights reserved.
Models, Inference and Algorithms
March 11, 2025
Broad Institute of MIT and Harvard
Primer: Heterogeneous reconstruction in cryo-EM
Rishwanth Raghu
Princeton University Department of Computer Science
Meeting: Machine learning for visualizing structural landscapes inside the cell
Ellen Zhong
Princeton University
Structural biology has been transformed by breakthroughs in deep learning methods for protein structure prediction. In parallel, advances in cryo-electron microscopy and tomography have produced new opportunities to study the dynamics and interactions of biomolecular complexes. In this seminar, I will describe the algorithmic challenges at the frontier of structure determination via cryo-EM. I will overview cryoDRGN, a machine learning system for heterogeneous cryo-EM and cryo-ET reconstruction. Along the way, I will overview recent progress in our group on reconstructing complex mixtures, developing a challenging benchmark for structural heterogeneity, and visualizing dynamic biomolecular complexes in situ.
Bio: Ellen Zhong is an Assistant Professor of Computer Science at Princeton University where she is also affiliated with the Princeton Laboratory for Artificial Intelligence, the Center for Statistics and Machine Learning, and the Omenn-Darling Bioengineering Institute. Her group’s research spans methodological research in AI and computer vision, as well as close collaboration with experimentalists in molecular and structural biology. Previously, she has worked on the AlphaFold team at Google DeepMind and at D. E. Shaw Research on molecular dynamics for drug discovery. She obtained her B.S. from the University of Virginia in 2014 and her Ph.D. from MIT in 2022 before joining the Princeton faculty.
For more information visit: broadinstitute.org/talks/spring-2025/mia
Copyright Broad Institute, 2024. All rights reserved.








![EWSC: Engineering sharper cancer immunotherapies using robotics and machine learning
Schmidt Center - MIT EECS Joint Colloquium Series
Presented by the Eric and Wendy Schmidt Center
March 9, 2026
Broad Institute of MIT and Harvard
Engineering sharper cancer immunotherapies using robotics and machine learning
Colloquium with Grégoire Altan-Bonnet
Deputy Chief, Laboratory of Integrative Cancer Immunology,
National Cancer Institute
Abstract:
Cancer immunotherapies elicit highly variable outcomes in patients and genetically identical mouse models, suggesting a strong intrinsic stochastic component. Using thousands of well-controlled ex vivo immunoassays, we show that leukocyte activation and tumor cytotoxicity display macroscopic variability that follows a shifted Poisson distribution. This variability arises from stochastic activation of a rare subpopulation of T cells (“Spark T cells”) coupled to a paracrine IFN-γ–driven positive feedback. By integrating these quantitative insights into a custom machine-learning pipeline with single-cell resolution, we phenotypically and functionally identify Spark T cells in murine naïve T cells and in human T cell blasts used for adoptive cell therapy, and demonstrate their role in shaping heterogeneous immunotherapy responses [http://dx.doi.org/10.2139/ssrn.4996071]. Building on this framework, we investigate how receptor-level signal integration modulates T cell potency and specificity. While chimeric antigen receptor (CAR) T cells show strong cytotoxicity but limited specificity in solid tumors, endogenous T cell receptors (TCRs) provide exquisite antigen discrimination with reduced efficacy. Deploying our high-throughput platform and mathematical modeling [PMID: 35587980], we reveal inhibitory and cooperative crosstalk between co-expressed TCRs and CARs: strong TCR–antigen interactions enhance CAR activation, whereas weak interactions antagonize it. Leveraging this crosstalk, we engineer dual TCR/CAR T cells targeting neoantigens and HER2 that exhibit enhanced antitumor activity with minimal off-tumor toxicity in a humanized solid tumor mouse model [PMID: 40220754] Together, these results show how stochastic T cell activation and receptor-level signal integration jointly govern variability, potency, and precision in cancer immunotherapy.
Questions? Email Amanda Ogden at aogden@broadinstitute.org.
Copyright Broad Institute, 2026. All rights reserved. EWSC: Engineering sharper cancer immunotherapies using robotics and machine learning](https://i.ytimg.com/vi/WzUd2_pQcyI/mqdefault.jpg)

