Anthony Vecchiarelli
@cellforganized.bsky.social
How do bacteria organize their innards?
Associate Prof at UMich
Associate Prof at UMich
The capacity to engineer both the composition of compartments and their positioning advances synthetic biology into a new era, where the spatial context of cellular function (“where”) can be programmed as readily as its content (“what”).
This was a massive team effort. Congrats to all authors!
This was a massive team effort. Congrats to all authors!
September 23, 2025 at 5:39 PM
The capacity to engineer both the composition of compartments and their positioning advances synthetic biology into a new era, where the spatial context of cellular function (“where”) can be programmed as readily as its content (“what”).
This was a massive team effort. Congrats to all authors!
This was a massive team effort. Congrats to all authors!
By fusing this MapTag to heterologous organelles and co-expressing McdA, we reprogramed the distribution of condensates, encapsulins, and even membrane-bound organelles in E. coli!
September 23, 2025 at 5:39 PM
By fusing this MapTag to heterologous organelles and co-expressing McdA, we reprogramed the distribution of condensates, encapsulins, and even membrane-bound organelles in E. coli!
We then repurposed McdAB as a generalized spatial regulator for other bacterial organelles. An N-terminal peptide of McdB is necessary and sufficient for McdA interaction. We developed this McdB peptide into a minimal autonomous positioning tag or “MapTag”.
September 23, 2025 at 5:39 PM
We then repurposed McdAB as a generalized spatial regulator for other bacterial organelles. An N-terminal peptide of McdB is necessary and sufficient for McdA interaction. We developed this McdB peptide into a minimal autonomous positioning tag or “MapTag”.
We also observed carboxysome “partitioning,” where the shell appears to invaginate at the midpoint of a larger carboxysome, suggesting that McdAB may play a role in carboxysome size regulation by subdividing oversized structures.
September 23, 2025 at 5:39 PM
We also observed carboxysome “partitioning,” where the shell appears to invaginate at the midpoint of a larger carboxysome, suggesting that McdAB may play a role in carboxysome size regulation by subdividing oversized structures.
Without McdAB, CryoET shows large and disorganized aggregates of carboxysome components at the cell poles. By contrast, McdAB-expressing cells displayed fully assembled, properly sized, and unclustered carboxysomes distributed across the nucleoid region of the cell!
September 23, 2025 at 5:39 PM
Without McdAB, CryoET shows large and disorganized aggregates of carboxysome components at the cell poles. By contrast, McdAB-expressing cells displayed fully assembled, properly sized, and unclustered carboxysomes distributed across the nucleoid region of the cell!
First, we showed that McdAB can distribute carboxysomes in E. coli!
September 23, 2025 at 5:38 PM
First, we showed that McdAB can distribute carboxysomes in E. coli!
Carboxysome organization is mediated by the Maintenance of Carboxysome Distribution (Mcd) system. McdB binds carboxysomes and induces McdA, a ParA-type ATPase, to oscillate along the nucleoid and distribute carboxysomes in the cell.
September 23, 2025 at 5:38 PM
Carboxysome organization is mediated by the Maintenance of Carboxysome Distribution (Mcd) system. McdB binds carboxysomes and induces McdA, a ParA-type ATPase, to oscillate along the nucleoid and distribute carboxysomes in the cell.
The most extensively studied bacterial organelle is the carboxysome, a protein-based organelle found in autotrophic bacteria that is responsible for significant global CO₂-fixation and holds promise for biotech applications.
September 23, 2025 at 5:38 PM
The most extensively studied bacterial organelle is the carboxysome, a protein-based organelle found in autotrophic bacteria that is responsible for significant global CO₂-fixation and holds promise for biotech applications.
We set out to determine if this conserved evolutionary strategy across diverse bacteria and cargo-types can be used a blueprint for engineering a generalizable method for programming spatial control in bacteria.
September 23, 2025 at 5:38 PM
We set out to determine if this conserved evolutionary strategy across diverse bacteria and cargo-types can be used a blueprint for engineering a generalizable method for programming spatial control in bacteria.
Bacteria encode self-organizing systems comprised of a ParA positioning ATPase and a partner protein that links these ATPases to diverse cellular cargoes. These modules distribute chromosomes, plasmids, protein complexes, and organelles across the bacterial world.
September 23, 2025 at 5:38 PM
Bacteria encode self-organizing systems comprised of a ParA positioning ATPase and a partner protein that links these ATPases to diverse cellular cargoes. These modules distribute chromosomes, plasmids, protein complexes, and organelles across the bacterial world.
This asymmetric distribution results in a loss of inheritance across the cell population, compromising activity and constraining applications.
September 23, 2025 at 5:38 PM
This asymmetric distribution results in a loss of inheritance across the cell population, compromising activity and constraining applications.
These compartments have drawn interest as modular building blocks for synthetic biology. Yet, a central challenge limits their use: when expressed in heterologous hosts such as E. coli, the nucleoid acts as a diffusion barrier.
September 23, 2025 at 5:38 PM
These compartments have drawn interest as modular building blocks for synthetic biology. Yet, a central challenge limits their use: when expressed in heterologous hosts such as E. coli, the nucleoid acts as a diffusion barrier.
In bacteria, protein-based microcompartments, encapsulins and condensates, as well as membrane-bound organelles, concentrate and regulate reactions without the complex endomembrane systems of eukaryotes.
September 23, 2025 at 5:38 PM
In bacteria, protein-based microcompartments, encapsulins and condensates, as well as membrane-bound organelles, concentrate and regulate reactions without the complex endomembrane systems of eukaryotes.
Lab made me a calendar for my bday. Here is July. Canadian tuxedos in full effect 🇨🇦
July 14, 2025 at 7:22 PM
Lab made me a calendar for my bday. Here is July. Canadian tuxedos in full effect 🇨🇦
We propose that, with ParA family ATPases, positioning and partitioning are mechanistically separable: weak interactions with the partner can mediate positioning, whereas effective partitioning requires stronger interactions capable of overcoming cargo self-association forces.
May 30, 2025 at 8:53 PM
We propose that, with ParA family ATPases, positioning and partitioning are mechanistically separable: weak interactions with the partner can mediate positioning, whereas effective partitioning requires stronger interactions capable of overcoming cargo self-association forces.
Our findings and math modelling suggest that weakened McdA–McdB interactions are sufficient to maintain carboxysome clusters on the nucleoid but inadequate for partitioning individual carboxysomes across it.
May 30, 2025 at 8:53 PM
Our findings and math modelling suggest that weakened McdA–McdB interactions are sufficient to maintain carboxysome clusters on the nucleoid but inadequate for partitioning individual carboxysomes across it.
We identify 3 Lys residues whose individual substitution modulates McdA binding and leads to distinct carboxysome organization phenotypes. Notably, Lys 7 substitutions result in a single carboxysome cluster at mid-nucleoid. Unlike an McdB deletion where carboxysomes cluster at the cell poles.
May 30, 2025 at 8:53 PM
We identify 3 Lys residues whose individual substitution modulates McdA binding and leads to distinct carboxysome organization phenotypes. Notably, Lys 7 substitutions result in a single carboxysome cluster at mid-nucleoid. Unlike an McdB deletion where carboxysomes cluster at the cell poles.
McdB belongs to a widespread but poorly characterized class of ParA partner proteins that connect it to the carboxysome cargo. The basis of its interaction with McdA remains unclear. We find that the N-terminal 20 residues of McdB are necessary and sufficient for interaction with McdA.
May 30, 2025 at 8:53 PM
McdB belongs to a widespread but poorly characterized class of ParA partner proteins that connect it to the carboxysome cargo. The basis of its interaction with McdA remains unclear. We find that the N-terminal 20 residues of McdB are necessary and sufficient for interaction with McdA.
The McdAB system spatially organize carboxysomes to promote efficient carbon fixation and ensure their equal inheritance during cell division. McdA, a ParA family ATPase, forms dynamic gradients on the nucleoid that position McdB-bound carboxysomes.
May 30, 2025 at 8:53 PM
The McdAB system spatially organize carboxysomes to promote efficient carbon fixation and ensure their equal inheritance during cell division. McdA, a ParA family ATPase, forms dynamic gradients on the nucleoid that position McdB-bound carboxysomes.
Huge thanks to Anthony Hyman for an outstanding Connell Lecture at the University of Michigan! 🌟 His talk on phase separation was both inspiring and thought-provoking. 👏🧪
From Cacio e Pepe to Proteins, phase separation is everywhere! 😜
@hymanlab.bsky.social
From Cacio e Pepe to Proteins, phase separation is everywhere! 😜
@hymanlab.bsky.social
May 7, 2025 at 1:58 PM
Huge thanks to Anthony Hyman for an outstanding Connell Lecture at the University of Michigan! 🌟 His talk on phase separation was both inspiring and thought-provoking. 👏🧪
From Cacio e Pepe to Proteins, phase separation is everywhere! 😜
@hymanlab.bsky.social
From Cacio e Pepe to Proteins, phase separation is everywhere! 😜
@hymanlab.bsky.social
We show that a compacted nucleoid maintains carboxysome organization in the absence of active McdAB-driven positioning. This finding reveals that the nucleoid is not merely a passive substrate for positioning, but an active player in spatial organization in bacteria.
April 25, 2025 at 6:52 PM
We show that a compacted nucleoid maintains carboxysome organization in the absence of active McdAB-driven positioning. This finding reveals that the nucleoid is not merely a passive substrate for positioning, but an active player in spatial organization in bacteria.