# Jesper Pallesen
Jesper Pallesen is a cryo-electron microscopist and structural biologist who works on ribosome dynamics, ion-channel structures, and structure-guided vaccine design.[1](https://www.wistar.org/our-scientists/jesper-pallesen/) He took his Ph.D. at Aarhus University, trained as a postdoctoral fellow in Nobel laureate [Joachim Frank](https://www.edgepedia.org/joachim-frank)'s cryo-EM group at Columbia University, and worked as a Research Associate at [Howard Hughes Medical Institute](https://www.edgepedia.org/howard-hughes-medical-institute) (HHMI) from 2009 to 2013; he is an Assistant Professor in the Vaccine & Immunotherapy Center at The Wistar Institute, with an affiliation recorded by the University of Pennsylvania.[1](https://www.wistar.org/our-scientists/jesper-pallesen/) • [2](https://www.wistar.org/blog/form-follows-function-jesper-pallesen-on-biology-the-structure-of-things/) • [3](https://www.linkedin.com/in/jesperpallesen) • [4](https://www.med.upenn.edu/apps/faculty/index.php/g20001280/p9734615) A note on his relationship to HHMI: reference databases sometimes list HHMI as his employer, but the retrieved record describes this as a specialist-level Research Associate position ending in January 2013, and no source describes a current HHMI investigator, group-leader, or staff-scientist appointment.[3](https://www.linkedin.com/in/jesperpallesen)
| Key fact | Detail |
|---|---|
| Field | Cryo-electron microscopy, structural biology, structural immunology[1](https://www.wistar.org/our-scientists/jesper-pallesen/) |
| Training | Ph.D. (nanotechnology), Aarhus University; postdocs with Joachim Frank at Columbia and at Scripps Research[1](https://www.wistar.org/our-scientists/jesper-pallesen/) • [2](https://www.wistar.org/blog/form-follows-function-jesper-pallesen-on-biology-the-structure-of-things/) |
| HHMI role | Research Associate (specialist), September 2009 to January 2013[3](https://www.linkedin.com/in/jesperpallesen) |
| Most cited work | Stabilized coronavirus spike (Scientific Reports, 2018, about 549 citations) and HIV-1 envelope spike (Nature, 2017, about 273 citations), per a self-authored profile; the 2014 PNAS ribosome paper has about 166 citations per iCite[3](https://www.linkedin.com/in/jesperpallesen) • [5](https://doi.org/10.1073/pnas.1419276111) |
| Landmark structure | High-resolution cryo-EM structure of human SWELL1 (LRRC8A), the volume-regulated anion channel (eLife, 2018), about 105 citations per iCite[6](https://doi.org/10.7554/eLife.38461) |
| Current positions | Assistant Professor, Vaccine & Immunotherapy Center, Wistar Institute; Wistar Institute Assistant Professor of Biochemistry and Biophysics at Penn[1](https://www.wistar.org/our-scientists/jesper-pallesen/) • [4](https://www.med.upenn.edu/apps/faculty/index.php/g20001280/p9734615) |
## Education and career path
Pallesen completed a nanotechnology Ph.D. at the University of Aarhus.[2](https://www.wistar.org/blog/form-follows-function-jesper-pallesen-on-biology-the-structure-of-things/) His cryo-EM training began as a postdoctoral fellow in Joachim Frank's group at Columbia University; Frank received the Nobel Prize for developing cryo-EM, and Pallesen spent five years there, leaving in 2013.[2](https://www.wistar.org/blog/form-follows-function-jesper-pallesen-on-biology-the-structure-of-things/) His HHMI appointment during this period was a Research Associate position in the Research department at specialist level, where he solved structures of functional biomacromolecular complexes relating to infectious diseases and designed software for electron-microscopy image processing.[3](https://www.linkedin.com/in/jesperpallesen)
After Columbia he took an unusual detour: he studied intellectual-property law as a paralegal, then moved to San Diego, where he earned an M.B.A. from the Rady School of Management at UC San Diego, specializing in statistics, finance, and management, while doing a second postdoc at [Scripps Research](https://www.edgepedia.org/scripps-research).[1](https://www.wistar.org/our-scientists/jesper-pallesen/) • [2](https://www.wistar.org/blog/form-follows-function-jesper-pallesen-on-biology-the-structure-of-things/) A bibliographic record places him in Scripps' Department of Integrative Structural and Computational Biology in [La Jolla](https://www.edgepedia.org/la-jolla) as of 14 August 2017.[7](https://cir.nii.ac.jp/crid/1380855568517992836) He also worked there as a Senior Research Associate on vaccine-related projects funded by HIVRAD, CAVD, IAVI, CHAVI-ID, VIC, the Gates Foundation, and NIH.[3](https://www.linkedin.com/in/jesperpallesen) His institutional pages place him as an Assistant Professor at [Indiana University Bloomington](https://www.edgepedia.org/indiana-university-bloomington) from January 2019, and at the Wistar Institute's Vaccine & Immunotherapy Center, where the University of Pennsylvania lists him as a Wistar Institute Assistant Professor of Biochemistry and Biophysics.[1](https://www.wistar.org/our-scientists/jesper-pallesen/) • [3](https://www.linkedin.com/in/jesperpallesen) • [4](https://www.med.upenn.edu/apps/faculty/index.php/g20001280/p9734615) Wistar and Penn pages list him as Wistar faculty, while a self-authored profile lists Indiana University Bloomington as current.[1](https://www.wistar.org/our-scientists/jesper-pallesen/) • [3](https://www.linkedin.com/in/jesperpallesen) • [4](https://www.med.upenn.edu/apps/faculty/index.php/g20001280/p9734615)
## Cryo-EM methods: particle picking and free-energy landscapes
Much of Pallesen's early output addresses two computational bottlenecks of single-particle cryo-EM. The first is particle selection. With Robert Langlois and colleagues he proposed a reference-free particle-selection method in 2011, augmented with a semi-supervised machine-learning algorithm to discriminate particles from contaminants and noise in micrographs where no reference volume is available.[8](https://doi.org/10.1016/j.jsb.2011.06.004) A 2014 follow-up with Langlois, John L. Rubinstein, and Joachim Frank presented an algorithm for low-contrast macromolecules that proved more effective than the human eye on close-to-focus micrographs, yielding improved or comparable resolution in reconstructions of two macromolecular complexes.[9](https://doi.org/10.1016/j.jsb.2014.03.001)
The second is motion reconstruction. Conventional pipelines sort particle snapshots into discrete classes and refine each to a static structure. The 2014 PNAS paper "Trajectories of the ribosome as a Brownian nanomachine", written with Ali Dashti, Peter Schwander, Robert Langlois, Hstau Y. Liao, Frank, and others, took a different route: it derived the free-energy landscape and continuous trajectories of a molecular machine directly from large numbers of cryo-EM snapshots.[5](https://doi.org/10.1073/pnas.1419276111) • [10](https://orcid.org/0000-0002-3270-1587) Applied to nontranslating ribosomes purified from yeast cells, the analysis revealed a closed path of low free energy along which the ribosome adopts conformational changes known to be associated with the elongation cycle, allowing model-free quantitative analysis of the degrees of freedom underlying continuous motions.[5](https://doi.org/10.1073/pnas.1419276111) The retrieved evidence describes the method only at the level of its abstract; independent comparative coverage of how it differs technically from classification-and-refinement pipelines is not available in the sources used here.
## Structuring the ribosome cycle
Pallesen's experimental cryo-EM work on the ribosome sits squarely in the Frank lineage. His most prominent structural paper in this area, published in eLife in 2013, presented the cryo-EM structure of a post-termination bacterial-type ribosome containing both the G-protein RF3 in its nucleotide-free (apo) state and the release factor RF1.[11](https://doi.org/10.7554/eLife.00411) Termination of messenger-RNA translation is initiated when RF1 or RF2 recognizes a stop codon in the ribosomal A site and releases the peptide; RF3 then promotes dissociation of the release factor.[11](https://doi.org/10.7554/eLife.00411) The structure showed that the conformation of RF3 differed from those of free RF3 bound to GDP and of ribosome-bound RF3 bound to a non-hydrolyzable GTP analog, and that RF1 adopted a conformation not seen in RF3-lacking complexes, providing structural keys to guanine-nucleotide exchange on RF3 and to an L12-mediated recruitment of RF3 to the ribosome.[11](https://doi.org/10.7554/eLife.00411)
## The volume-regulated anion channel structure
In 2018, Pallesen co-authored a high-resolution cryo-EM structure of full-length human homo-hexameric SWELL1 (LRRC8A), the only essential subunit of the volume-regulated anion channel (VRAC), which regulates cellular volume homeostasis and is activated by hypotonic solutions.[6](https://doi.org/10.7554/eLife.38461) The structure revealed a trimer of dimers assembly with a symmetry mismatch between the pore-forming domain and the cytosolic leucine-rich repeat domains.[6](https://doi.org/10.7554/eLife.38461) [Mutational analysis](https://www.edgepedia.org/mutational-analysis) showed that a charged residue at the narrowest constriction of the homomeric channel is an important pore determinant of heteromeric VRAC, and a mutation in the flexible N-terminal portion of SWELL1 affected pore properties, suggesting a link between intracellular structures and channel regulation.[6](https://doi.org/10.7554/eLife.38461) Because SWELL1 can combine with four other LRRC8 family members into a heterogeneous cohort of channels with different properties, the structure served as a scaffold for dissecting VRAC heterogeneity and activation; this work has drawn about 105 citations per iCite.[6](https://doi.org/10.7554/eLife.38461)
## HIV and coronavirus structural immunology
Pallesen's methods range beyond cryo-EM. In 2011 he used atomic force microscopy to visualize the dimer formed by RNAs spanning HIV-1 nucleotides 1-744, finding a distinct ring morphology implying a dimer held together at two dimer-linkage sites, one containing the TAR element and one containing the DIS dimerization-initiation site.[12](https://doi.org/10.1021/bi200488h) During his Scripps years on HIV and pandemic-preparedness consortia he contributed structural work on viral envelope glycoproteins; his most-cited papers include a 2017 Nature paper on the HIV-1 envelope spike (about 273 citations) and a 2018 [Scientific Reports](https://www.edgepedia.org/scientific-reports) paper on a stabilized coronavirus spike (about 549 citations) per his self-authored profile.[3](https://www.linkedin.com/in/jesperpallesen)
His current laboratory continues this line with structure-guided immunogen design. In the 2026 Nature Immunology WIN332 study, an engineered HIV-1 Env immunogen elicited a new class of Asn332-glycan-independent antibodies against the conserved V3-glycan epitope after a single bolus immunization in nonhuman primates; the study's electron-microscopy polyclonal epitope mapping of serum antibodies and cryo-EM analysis showed that the elicited antibodies resemble the most potent human type-I and type-II V3-glycan broadly neutralizing antibodies in sequence and binding.[13](https://doi.org/10.1038/s41590-025-02408-z)
## Recent developments
His recent work includes HIV Env immunogen design, with the WIN332 line continuing through the 2026 Nature Immunology paper.[13](https://doi.org/10.1038/s41590-025-02408-z) His post-2023 institutional base is a matter of conflicting records: Wistar and Penn list him as Wistar faculty, while his own profile lists Indiana University Bloomington (assistant professor since January 2019, based in Haverford, Pennsylvania); neither record supports a current HHMI role.[1](https://www.wistar.org/our-scientists/jesper-pallesen/) • [3](https://www.linkedin.com/in/jesperpallesen) • [4](https://www.med.upenn.edu/apps/faculty/index.php/g20001280/p9734615)
## References
1. [Jesper Pallesen, MBA, Ph.D. - The Wistar Institute](https://www.wistar.org/our-scientists/jesper-pallesen/)
2. [Jesper Pallesen on Biology & the Structure of Things | Wistar](https://www.wistar.org/blog/form-follows-function-jesper-pallesen-on-biology-the-structure-of-things/)
3. [Jesper Pallesen - LinkedIn profile](https://www.linkedin.com/in/jesperpallesen)
4. [Jesper Pallesen | Perelman School of Medicine, University of Pennsylvania](https://www.med.upenn.edu/apps/faculty/index.php/g20001280/p9734615)
5. [Trajectories of the ribosome as a Brownian nanomachine (PNAS, 2014)](https://doi.org/10.1073/pnas.1419276111)
6. [Structure of the human volume regulated anion channel (eLife, 2018)](https://doi.org/10.7554/eLife.38461)
7. [Jesper Pallesen | CiNii Research](https://cir.nii.ac.jp/crid/1380855568517992836)
8. [Reference-free particle selection enhanced with semi-supervised machine learning for cryo-electron microscopy (J Struct Biol, 2011)](https://doi.org/10.1016/j.jsb.2011.06.004)
9. [Automated particle picking for low-contrast macromolecules in cryo-electron microscopy (J Struct Biol, 2014)](https://doi.org/10.1016/j.jsb.2014.03.001)
10. [Jesper Pallesen (0000-0002-3270-1587) - ORCID](https://orcid.org/0000-0002-3270-1587)
11. [Cryo-EM visualization of the ribosome in termination complex with apo-RF3 and RF1 (eLife, 2013)](https://doi.org/10.7554/eLife.00411)
12. [Structure of the HIV-1 5' untranslated region dimer alone and in complex with gold nanocolloids (Biochemistry, 2011)](https://doi.org/10.1021/bi200488h)
13. [Rapid elicitation of neutralizing Asn332-glycan-independent antibodies to the V3-glycan epitope of HIV-1 Env in nonhuman primates (Nat Immunol, 2026)](https://doi.org/10.1038/s41590-025-02408-z)
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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in structural biology, biochemistry, and biophysics › Cryo-electron microscopy*
*Initially written Sep 17, 2026 · Edited: Oct 11, 2026; Oct 15, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license