Biology subjects

Hesselberth, J.

Publications and source records attributed to Hesselberth, J..

4 recordsLinked to original sources

bioRxiv2025

Big1 is a cell cycle regulator linking cell size to basal body number

Cell size control in dividing cells coordinates cell growth with cell division. In the ciliated protozoan, Tetrahymena, there is a tight link between cell size and the cytoskeletal assemblies at the cell cortex organized around basal bodies (BBs). BBs dictate the distribution of ciliary units governing cell motility and are organized into 18-22 ciliary rows. The number of BBs per cell remains remarkably consistent even when the number and lengths of ciliary rows vary. big1-1 mutant cells are large and have elevated numbers of BBs, providing a system to investigate links between BB number and cell size control. We discovered BIG1 encodes a protein with an RRM3 RNA-binding domain similar to the fission yeast meiotic entry gene, mei2. The big1-1 mutation is a predicted null allele. By extending the duration of specific cell cycle stages conducive to new BB assembly, big1-1 promotes cell size increases through BB amplification. In contrast, excess Big1 protein localizes to BBs and drives cells into premature cell division, resulting in small cells with fewer BBs. Thus, Tetrahymena Big1 localizes to BBs and controls cell cycle progression, indicating BBs and Big1 link cell growth to the cell division cycle.

cell biology↗

bioRxiv2024

A specific and portable gene expression program underlies antigen archiving by lymphatic endothelial cells

Antigens from protein subunit vaccination traffic from the tissue to the draining lymph node, either passively via the lymph or carried by dendritic cells at the local injection site. Lymph node (LN) lymphatic endothelial cells (LEC) actively acquire and archive foreign antigens, and archived antigen can be released during subsequent inflammatory stimulus to improve immune responses. Here, we answer questions about how LECs achieve durable antigen archiving and whether there are transcriptional signatures associated with LECs containing high levels of antigen. We used single cell sequencing in dissociated LN tissue to quantify antigen levels in LEC and dendritic cell populations at multiple timepoints after immunization, and used machine learning to define a unique transcriptional program within archiving LECs that can predict LEC archiving capacity in independent data sets. Finally, we validated this modeling, showing we could predict antigen archiving from a transcriptional dataset of CHIKV infected mice and demonstrated in vivo the accuracy of our prediction. Collectively, our findings establish a unique transcriptional program in LECs that promotes antigen archiving that can be translated to other systems.

immunology↗

bioRxiv2023

Chikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO

Infection with chikungunya virus (CHIKV) causes disruption of draining lymph node (dLN) organization, including paracortical relocalization of B cells, loss of the B cell-T cell border, and lymphocyte depletion that is associated with infiltration of the LN with inflammatory myeloid cells. Here, we find that during the first 24 h of infection, CHIKV RNA accumulates in MARCO-expressing lymphatic endothelial cells (LECs) in both the floor and medullary LN sinuses. The accumulation of viral RNA in the LN was associated with a switch to an antiviral and inflammatory gene expression program across LN stromal cells, and this inflammatory response, including recruitment of myeloid cells to the LN, was accelerated by CHIKV-MARCO interactions. As CHIKV infection progressed, both floor and medullary LECs diminished in number, suggesting further functional impairment of the LN by infection. Consistent with this idea, we find that antigen acquisition by LECs, a key function of LN LECs during infection and immunization, was reduced during pathogenic CHIKV infection.

immunology↗

bioRxiv2020

Custom-Designed, Degradation-Resistant Messenger RNAs in Yeast

Virally-derived RNA structures provide useful tools for engineering messenger RNA (mRNA) transcripts with unique properties. Here we show that 5[->]3 exoribonuclease-resistant RNA structures (xrRNAs) from Flaviviruses can be used to protect heterologously-expressed messenger RNAs (mRNAs) from 5[->]3 degradation in Saccharomyces cerevisiae (budding yeast). Installation of xrRNAs ahead of a downstream internal ribosome entry site (IRES) leads to the accumulation of partially-degraded mRNAs designed to undergo cap-independent translation. In a yeast strain favoring cap-independent translation, this strategy led to a 30-fold increase in the enzymatic activity of lysates obtained from cells expressing degradation-resistant reporters. Overall, these finding demonstrate the possibility of coupling multiple viral RNA structures together to enhance protein expression.

biochemistry↗