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"Pattern Formation and Regeneration in a Single Cell"

A headshot of Dr. Wallace Marshall.Dr. Wallace Marshall | Marshall Lab

Bio:
Wallace Marshall is professor of biochemistry and biophysics at the University of California, San Francisco. A native Long Islander, he received his bachelor’s degrees in electrical engineering and biochemistry from the State University of New York at Stony Brook and his Ph.D. in biochemistry from UC San Francisco, where he studied organization of chromosomes within the nucleus with John Sedat. He then moved to Yale University for postdoctoral studies with Joel Rosenbaum, where he became interested in questions of organelle size control and cell organization, using cilia, flagella and centrioles as model systems. 

In 2003, he joined the faculty at UCSF, where he continues to study questions of cellular organization in a variety of model organisms including green algae, yeast, ciliates and mammalian cells. In recent years, his research program has expanded to include cellular engineering and the study of learning and computation in single cells. Marshall is an elected fellow of the American Society for Cell Biology, former co‐director of the physiology summer course at the Marine Biological Laboratory in Woods Hole, Massachusetts, and he currently is director of the Center for Cellular Construction, an NSF Science and Technology Center, devoted to engineering cells and tissues.

Abstract:
Cells are sometimes viewed as small, simple building blocks for more complex organisms, but in fact individual cells can have extremely complex structures. Where does the information come from to build patterns within a single shared cytoplasm? We view this as essentially a question of developmental biology, but now at the sub-cellular level. 

To understand how developmental processes work within a single cell, we have turned to the classical model organism Stentor coeruleus. Stentor is a giant ciliate with a size and complexity comparable to an animal embryo and has extraordinary powers of regeneration that classically allowed surgical manipulations similar to those used to for studying development in embryos. We have sequenced the Stentor genome and developed methods to perturb gene expression.  

Our current work focuses on two questions: 

  • How does the cell sense when it is necessary to regenerate?
  • How does the cell build and maintain patterns corresponding to the major body axes?

Using a combination of genomics, proteomics, and microscopy methods, we have begun to make progress in both directions. We find that the initiation of regeneration appears to involve a cell cycle transition governed by the Cdk4/cyclin D - E2F pathway as well as by MAPK signaling. Development of spatial pattern appears to involve non-random distribution of cytoskeletal scaffolding proteins and localization of mRNA encoding both structural proteins and potential transcription factors, possibly suggesting a role for localized differences in gene expression within the highly polyploid macronucleus.

Images of Stentor coeruleus. left panel transmitted light micrograph of live Stentor cell.  right panel anatomical drawing of Stentor showing a ring of cilia at the top and a holdfast at the bottom, taken from Tartar 1961 The Biology of Stentor.

Date:
Location:
THM 116

"Decoding Gene Regulation During CNS Repair"

A headshot of Dr. Llorens Bobadilla.Dr. Enric Llorens Bobadilla | Llorens Bobadilla Lab

Bio:
Enric Llorens-Bobadilla is an assistant professor and group leader at the Department of Cell and Molecular Biology at Karolinska Institutet in Stockholm, Sweden. His lab, established in 2022, focuses on understanding glial biology and developing regenerative strategies for the central nervous system, leveraging single-cell and spatial genomics technologies.

Llorens-Bobadilla earned his Ph.D. from the University of Heidelberg and the German Cancer Research Center (DKFZ) in Germany, where he pioneered single-cell transcriptomic approaches to study adult stem cell niches. He then completed postdoctoral training with Jonas Frisén at Karolinska Institutet as a Human Frontier Science Program fellow.

He is the recipient of an ERC Starting Grant, was named a Wallenberg Academy Fellow and received the Swedish Foundation for Strategic Research Future Leaders award.

Abstract:
Injuries to the central nervous system cause permanent disability in mammals because resident cells fail to mount an effective regenerative response. In this talk, I will present our recent studies investigating how glial cells, particularly astrocytes and ependymal cells, respond to spinal cord injury, and what gene-regulatory mechanisms govern their regenerative potential. 

I will first show that ependymal-derived neural stem cells in the injured spinal cord possess a latent lineage potential that, while not manifested under normal conditions, can be unlocked to produce new oligodendrocytes, promote remyelination and restore axon conduction. I will then describe how we mapped the enhancer landscape of the injury response across glial cell types, revealing that injury-responsive enhancers encode cell-type specificity by integrating stress-response and cell-identity transcription factor programs, a logic that enables precision targeting of reactive astrocytes using gene therapy vectors. 

Finally, I will present a cross-species comparison at single cell resolution between the regeneration-competent spiny mouse (Acomys) and the laboratory mouse (Mus). While both species activate similar injury-response programs, cells in Acomys rapidly resolve their reactive state whereas those in Mus remain permanently altered. These findings suggest that the reversibility of injury-induced gene-regulatory changes, rather than the initial response itself or a large regulatory rewiring, may be a critical determinant of regenerative success. Together, these studies uncover mechanisms that limit the regenerative potential of glial cells in mammals and identify potential precision interventions to promote spinal cord repair.

Zamboni, M, Martínez Martín, A., Rydholm, G., Häneke, T., Pintado, L., Secilmis. D., Ziegenhain, C., Llorens-Bobadilla, E. (2025) The regulatory code of injury responsive enhancers enables precision cell state targeting in the CNS. Nature Neuroscience. DOI: doi-org.proxy.kib.ki.se/10.1038/s41593-025-02131-w

Llorens-Bobadilla, E.#, Zamboni, M., Marklund, M., Bhalla, N., Chen, X., et al. (2023). Solid-phase capture and profiling of open chromatin by spatial ATAC. Nature Biotechnology, 41(8), 1085-1088. 

Llorens-Bobadilla, E., Chell, J.M., Le Merre, P., Wu, Y., Zamboni, M., et al. (2020). A latent lineage potential in resident neural stem cells enables spinal cord repair. Science, 370(6512), eabb8795. 

View Dr. Llorens Bobadilla CV here!

Watch the seminar here.

Figure. Confocal image of a horizontal section of an injured mouse spinal cord. GFAP astrocytes stained in gray, intravenous tracer in magenta scale.

Date:
Location:
THM 116

"The Role of Epigenetic Potential in House Sparrow Range Expansions"

A photo of Dr. Martin holding a bird outside with some greenery in the background.Dr. Lynn Martin | Martin Lab

Bio:
Dr. Lynn B. Martin is a professor of global, environmental and genomic health sciences in the College of Public Health at the University of South Florida. He earned his B.S. and M.S. in biology from Virginia Commonwealth University and completed his M.A. and Ph.D. in ecology and evolutionary biology at Princeton University, followed by postdoctoral training in psychology and neuroscience at The Ohio State University.

His research focuses on physiological ecology, disease ecology and ecological epigenetics, with an emphasis on how organisms respond to environmental change. Much of his work uses wild vertebrates — especially birds and small mammals — to understand how variation in immune function, hormones and gene regulation shapes health, host competence and adaptation in natural populations.

Abstract:
Why do some populations colonize new areas whereas others fail? This question is becoming more and more important to answer as we continue to change the planet. For about two decades, my lab has been studying how one of the world’s most common species, the house sparrow, has achieved its success. Whereas we have considered a variety of behavioral and physiological mechanisms, we are finding that one epigenetic process, namely the regulation of gene expression via DNA methylation, was particularly important. In this talk, I’ll present highlights of our current work on how the interplay of foraging behavior, infection with gut pathogens and physiological defenses has enabled some birds to found new populations and hence colonize many parts of the world.

Date:
Location:
THM 116
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