Biology subjects

Engel, B.

Publications and source records attributed to Engel, B..

5 recordsLinked to original sources

bioRxiv2026

RBMP2 shapes specialized membranes for CO₂ delivery in the pyrenoid condensate

Approximately one-third of global CO2 fixation occurs in the algal pyrenoid, a condensate of the CO2-fixing enzyme Rubisco traversed by membranes that supply it with CO2. In the model alga Chlamydomonas reinhardtii, CO2 is delivered by a specialized central reticulated region of these membranes. Here we define how this region is built and identify RBMP2 as the first factor required for its biogenesis. Loss of RBMP2 prevents reticulated-region formation and impairs pyrenoid-dependent growth. RBMP2 domains perform separable roles in extending membrane tubules toward the pyrenoid center and remodeling them into narrow tubules of the reticulated region. The CO2-releasing carbonic anhydrase CAH3 localizes not only to the reticulated region but also to helical interfaces between tubules and minitubules, which expand in some RBMP2 truncation mutants. Our findings advance the basic understanding of pyrenoid function and establish the pyrenoid as a powerful system for studying membrane remodeling within a phase-separated condensate.

Plant Biology↗

bioRxiv2026

Mature plant chloroplasts form reversible gyroid cubic membranes

Across kingdoms, cells fold their membranes into precise shapes closely linked to their functions. In mature land-plant chloroplasts, the photosynthetic membranes have been viewed as strictly lamellar and it is unknown whether they can take on a different structure while remaining functional. Here, we show that mature Arabidopsis thaliana chloroplasts can transform this network into a gyroid-type cubic membrane, which we call the gyrobody. The gyrobody forms reversibly during the night and preserves photosystem II photochemistry. A decrease in stromal side thylakoid surface charge, caused by lower protein phosphorylation, triggers the lamellar-to-gyroid transition which the curvature-inducing lipid MGDG facilitates. This shows that the mature plant thylakoid network is not locked into its lamellar form, revealing unexpected structural flexibility of this system.

Plant Biology↗

bioRxiv2026

Profound CD4+ T-Cell Reprogramming by Melphalan-Driven Oxidative Stress in High-Risk Multiple Myeloma

T cell-based immunotherapies have become central to the treatment of multiple myeloma (MM), yet their efficacy depends on the functionality of endogenous T cells. How cumulative treatment exposure, particularly high-dose melphalan, together with disease-intrinsic high-risk features shapes T-cell composition and immune competence remains incompletely understood. Here, we analyzed T cell composition and function in bone marrow (BM) and peripheral blood (PB) samples from MM patients across different stages of their treatment journey using flow cytometry (BM, n=162; PB, n=1,733), single-cell RNA sequencing (n=19), and cytotoxicity assays (n=20). We reveal reduced overall T cell frequencies and CD4+/CD8+ T cell ratio, associated with lines of therapy and driven in part by depletion of naive CD4+ T cells in gene-expression defined high risk (HR) disease. Among therapeutic agents, melphalan exerted the strongest effects on T cell populations and induced pronounced redox stress in both T cells and myeloma cell lines. This oxidative stress signature was enriched in HR patients and was reversible with N-acetyl-L-cysteine treatment. Together, these findings identify immune dysregulation as a defining feature of HR MM that extends beyond tumor-intrinsic genomic alterations and is further shaped by treatment-induced remodeling of the BM microenvironment. Given the association between higher CD4+ T cell numbers and improved CAR-T cell outcomes, our data highlight the translational importance of treatment sequencing, particularly in HR MM. One Sentence SummaryMelphalan-induced redox stress depletes CD4+ naive T cells, particularly in patients with high-risk multiple myeloma.

Cancer Biology↗

bioRxiv2026

Sticker number modulates pyrenoid condensate assembly to support algal fitness

The valency of intrinsically disordered proteins underpins liquid-liquid phase separation (LLPS), yet how this parameter shapes condensate function and cellular fitness remains poorly understood. Here we exploit the algal pyrenoid-a minimal, two component LLPS system-to directly link condensate properties to physiological performance. Pyrenoid assembly is driven by a disordered, multivalent Linker protein that binds Rubisco at symmetry-related surface sites, with the number of binding motifs ("stickers") varying across species. Using Chlamydomonas reinhardtii, we systematically tuned sticker number from two to nine and examined effects on Rubisco condensation, pyrenoid architecture and CO2 fixation. Three stickers were sufficient for condensation in vitro, but at least four were required for pyrenoid assembly in vivo. Cryo-electron tomography and single-molecule tracking revealed that increasing sticker number enhances Rubisco packing and mobility, while time-resolved imaging and competition assays demonstrated that sticker number governs the kinetics of pyrenoid formation and determines cellular fitness under fluctuating carbon conditions. Our findings establish sticker number as an evolutionary tuning parameter that balances condensate formation, dynamics, and function, providing a quantitative framework for linking the molecular grammar of phase separation to biological fitness.

cell biology↗

bioRxiv2025

Targeted Molecular MRI of Colorectal Cancer by Antibody Functionalized Hyperpolarized Silicon Particles

The development of non-invasive, non-ionizing sensitive molecular targeting approaches to detect colorectal cancer (CRC) lesions is warranted to improve high risk patient outcomes. Hyperpolarized silicon nanoparticles and microparticles are potentially well-suited to act as targeted molecular imaging agents because of their overall biocompatibility and long-lasting enhanced magnetic resonance imaging (MRI) signals. In this study, dynamic nuclear polarization was performed on silicon particles functionalized with an antibody to Mucin-1 (MUC1), a surface mucin glycoprotein aberrantly expressed in CRC. Antibody conjugation to the particle surface did not affect 29Si hyperpolarization characteristics. Similarly, conjugation and the dynamic nuclear polarization process did not adversely affect the affinity of the targeting antibody. In vivo MRI scans performed 10-15 minutes after luminal administration of targeted hyperpolarized particles into human MUC1-expressing orthotopic CRC mouse models showed that particles actively targeted tumor sites. These results were supported by chemical and biological controls and blocking experiments as well as correlative immunohistochemical analysis. These surface-functionalized silicon particles are under development as a platform technology that will allow non-invasive molecular targeting of CRC using hyperpolarized MRI. Single Sentence SummaryTargeted molecular MR imaging of colorectal cancer by hyperpolarized silicon particles functionalized with mucin 1 antibody.

cancer biology↗