André Nadler
@nadlerlab.bsky.social
Chemist in a CellBio place. Fan of lipids & membranes
Lipid imaging on the cover of @nature.com! Great times for lipid cell biology indeed. And a fantastic recognition of all the hard work by the team, especially Juan M. Iglesias-Artola and Kristin Böhlig (who made the cover). Link to article: www.nature.com/articles/s41...
October 9, 2025 at 9:01 AM
Lipid imaging on the cover of @nature.com! Great times for lipid cell biology indeed. And a fantastic recognition of all the hard work by the team, especially Juan M. Iglesias-Artola and Kristin Böhlig (who made the cover). Link to article: www.nature.com/articles/s41...
Organelle lipid compositions could also be controlled by local metabolism, but we find that lipid transport is up to 60 times faster than metabolism, all but ruling out this possibility.
August 21, 2025 at 5:19 AM
Organelle lipid compositions could also be controlled by local metabolism, but we find that lipid transport is up to 60 times faster than metabolism, all but ruling out this possibility.
Even more exciting: Not only does the transport become much slower, the steady state distribution of the substrate lipid shifts, a hallmark of an active process.
August 21, 2025 at 5:19 AM
Even more exciting: Not only does the transport become much slower, the steady state distribution of the substrate lipid shifts, a hallmark of an active process.
And indeed, there is a major effect on lipid transport in a flippase knockdown.
August 21, 2025 at 5:19 AM
And indeed, there is a major effect on lipid transport in a flippase knockdown.
Organelle lipid compositions are very different, the energy for maintaining these gradients has to come from somewhere. An exciting hypothesis is that lipid flippases (ATPases) and scramblases are part of the answer.
August 21, 2025 at 5:19 AM
Organelle lipid compositions are very different, the energy for maintaining these gradients has to come from somewhere. An exciting hypothesis is that lipid flippases (ATPases) and scramblases are part of the answer.
Furthermore, non-vesicular lipid transport is *much* more specific than vesicular transport. The differences in transport rates between closely related lipid species are huge!
August 21, 2025 at 5:19 AM
Furthermore, non-vesicular lipid transport is *much* more specific than vesicular transport. The differences in transport rates between closely related lipid species are huge!
Our first discovery was that on-vesicular lipid transport is much faster than vesicular transport, shown here for the average transport rates for all probes tested.
August 21, 2025 at 5:19 AM
Our first discovery was that on-vesicular lipid transport is much faster than vesicular transport, shown here for the average transport rates for all probes tested.
Here’s an example for to Phosphatidylcholine species that differ only in one fatty acid chain:
August 21, 2025 at 5:19 AM
Here’s an example for to Phosphatidylcholine species that differ only in one fatty acid chain:
Having these kinds of data allows you to draw up and actually fit rather complex kinetic models to the data (Thanks Björn!):
August 21, 2025 at 5:19 AM
Having these kinds of data allows you to draw up and actually fit rather complex kinetic models to the data (Thanks Björn!):
Quantification works by four-color imaging with organelle markers (more troubleshooting), machine-learning assisted image analysis and fluorescence signal assignment to organelles:
August 21, 2025 at 5:19 AM
Quantification works by four-color imaging with organelle markers (more troubleshooting), machine-learning assisted image analysis and fluorescence signal assignment to organelles:
Overall, this works really well (after an unfortunate amount of time spent troubleshooting, the project started 10 years ago):
August 21, 2025 at 5:19 AM
Overall, this works really well (after an unfortunate amount of time spent troubleshooting, the project started 10 years ago):
These probes are delivered into the outer plasma membrane leaflet, and used in pulse chase experiments. A LOT of work went into optimizing UV crosslinking, click-chemistry labelling and imaging to achieve the required time resolution.
August 21, 2025 at 5:19 AM
These probes are delivered into the outer plasma membrane leaflet, and used in pulse chase experiments. A LOT of work went into optimizing UV crosslinking, click-chemistry labelling and imaging to achieve the required time resolution.
We use bifunctional, minimally modified lipids that bear diazirine (for photocrosslinking) and alkyne (for labelling) moieties:
August 21, 2025 at 5:19 AM
We use bifunctional, minimally modified lipids that bear diazirine (for photocrosslinking) and alkyne (for labelling) moieties:
Out today in @nature.com: Together with the Honigmann, Shevchenko, Drobot and Hof labs, we present a general workflow for imaging the localization and transport of individual lipids in cells and mapping their metabolism.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
August 21, 2025 at 5:19 AM
Out today in @nature.com: Together with the Honigmann, Shevchenko, Drobot and Hof labs, we present a general workflow for imaging the localization and transport of individual lipids in cells and mapping their metabolism.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
You’re not actually interested in calcium? GEQO is a modular platform compared to earlier forms of similar designs. By simply swapping the sensor domain for another green fluorescent biosensor, you can create a GEQO sensor for your favourite small molecule. We report GEQO variants for cAMP and ATP.
May 13, 2025 at 8:40 AM
You’re not actually interested in calcium? GEQO is a modular platform compared to earlier forms of similar designs. By simply swapping the sensor domain for another green fluorescent biosensor, you can create a GEQO sensor for your favourite small molecule. We report GEQO variants for cAMP and ATP.
We report a parametrization strategy for single cell signalling transients. Using this approach, we show that absolute quantification retains information in time trace data that is lost in other data analysis strategies.
May 13, 2025 at 8:40 AM
We report a parametrization strategy for single cell signalling transients. Using this approach, we show that absolute quantification retains information in time trace data that is lost in other data analysis strategies.
The analyte independent reference fluorophore does not just make the sensor ratiometric, it allows for direct quantification of single cell GEQO expression levels. This provides an in-built control for common perturbations introduced by the biosensors themselves, like analyte buffering.
May 13, 2025 at 8:40 AM
The analyte independent reference fluorophore does not just make the sensor ratiometric, it allows for direct quantification of single cell GEQO expression levels. This provides an in-built control for common perturbations introduced by the biosensors themselves, like analyte buffering.
Using purified GEQO protein, we generated a set of calibration curves to retrieve absolute concentrations of the GEQO sensor and its analyte calcium inside the living cell.
May 13, 2025 at 8:40 AM
Using purified GEQO protein, we generated a set of calibration curves to retrieve absolute concentrations of the GEQO sensor and its analyte calcium inside the living cell.
GEQO sensors combine FRET-like ratiometric imaging with the performance of single fluorophore sensors. With single wavelength excitation and a reference channel that does not change its fluorescence intensity with analyte concentration, GEQO sensors can be used on any common imaging platform.
May 13, 2025 at 8:40 AM
GEQO sensors combine FRET-like ratiometric imaging with the performance of single fluorophore sensors. With single wavelength excitation and a reference channel that does not change its fluorescence intensity with analyte concentration, GEQO sensors can be used on any common imaging platform.
Meet GEQO: Genetically-encoded biosensors for absolute small-molecule quantification in single cells brought to you by @sascha-kuhn.bsky.social. For simple absolute quantification of your favourite small molecule or ion, head on over to @bioarxiv and read our new preprint: doi.org/10.1101/2025...
May 13, 2025 at 8:40 AM
Meet GEQO: Genetically-encoded biosensors for absolute small-molecule quantification in single cells brought to you by @sascha-kuhn.bsky.social. For simple absolute quantification of your favourite small molecule or ion, head on over to @bioarxiv and read our new preprint: doi.org/10.1101/2025...
The most likely explanation for high lipid transbilayer flux at steady state: The transbilayer lipid concentration gradient functions similarly to other (ion or proton) concentration gradients, as a store of potential energy or a cellular battery.
May 6, 2025 at 9:01 AM
The most likely explanation for high lipid transbilayer flux at steady state: The transbilayer lipid concentration gradient functions similarly to other (ion or proton) concentration gradients, as a store of potential energy or a cellular battery.
Metabolism is shifted to catabolic processes and biomass production is down: This suggests that perturbing lipid asymmetry places a significant strain on the cellular energy budget, which implies considerable ATP usage by flippases at steady state and high lipid transbilayer flux at steady state.
May 6, 2025 at 9:01 AM
Metabolism is shifted to catabolic processes and biomass production is down: This suggests that perturbing lipid asymmetry places a significant strain on the cellular energy budget, which implies considerable ATP usage by flippases at steady state and high lipid transbilayer flux at steady state.
Time to get fancy & take a quantitative look at things and used isothermal microcalorimetry to measure dissipated heat and quantitative phase contrast microscopy to measure cell growth. The result was clear. The cells used more energy to make less biomass.
May 6, 2025 at 9:01 AM
Time to get fancy & take a quantitative look at things and used isothermal microcalorimetry to measure dissipated heat and quantitative phase contrast microscopy to measure cell growth. The result was clear. The cells used more energy to make less biomass.
We looked at cellular energy expenditure in a number of different ways – monitored lipid droplet dynamics, followed ATP depletion with biosensors and measure oxygen consumption rates. All assays said the same thing: Energy use is up and overall cellular energy usage is altered in a major way.
May 6, 2025 at 9:01 AM
We looked at cellular energy expenditure in a number of different ways – monitored lipid droplet dynamics, followed ATP depletion with biosensors and measure oxygen consumption rates. All assays said the same thing: Energy use is up and overall cellular energy usage is altered in a major way.
On the lipid side, we found that triacylglycerols, prototypical energy storage lipids were consistently lower, in line with higher energy use.
May 6, 2025 at 9:01 AM
On the lipid side, we found that triacylglycerols, prototypical energy storage lipids were consistently lower, in line with higher energy use.