Jupiter Algorta

Investigating Local Negative Feedback of Rac Activity by Mathematical Models and Cell Motility Simulations For polarization and directed migration, cells use a combination of local positive feedback and long-range inhibition. We have previously used mathematical models to show the ability of this core…

If you're curious about how cells make decisions in complex environments, and how mathematical models can capture such behaviour, our preprint is now live!
Check it out here: www.biorxiv.org/content/10.1...

Following a hypothesis proposed by Orion and Jason, I tested multiple models and formalisms to explain how cell reversal could be explained.
The key was adding a negative feedback loop (a Rac inhibitor) to the molecules driving cell motion.
With this, simulations finally matched experiments.

But when the light expands from part of the cell to illuminate the whole cell, real cells reverse rotation, something previous model(s) failed to predict.
This and other puzzling results led us to revise such models to better understand how cells reorient.

When the light hits one side of the cell, it smoothly reorients toward it.
In simple environments, a previous polarity model captured this motion well.

In 2023, Dr. Orion Weiner and Dr. Jason Town (UCSF) showed how to guide cells with light, using “optogenetic” stimulation upstream of Rac t o steer neutrophils .
Before diving deeper, here’s what you’ll see:
Left = experiment, right = simulation.
Green = cell edge, blue = light stimulus.

Previous models of cell polarity capture basic movements, but not flexibility. When the chemical signal changes direction, they stay locked in place. Our revised model (right) reorients and tracks the new direction. We’re releasing the full story today as a preprint – link below.

A cell navigating a chemical gradient is like being blindfolded in a dense forest, trying to find a clearing by feeling slight changes in the breeze. No map, no clear path. And yet, immune cells can find their way. I build models to understand how.

Check this fascinating footage: a neutrophil navigating towards a micropipette. These cells can not only navigate complex, noisy environments, but also rapidly reorient to new cues. Curious about how they do it? Keep reading!

In 2023, Dr. Orion Weiner and Dr. Jason Town (UCSF) showed how to guide cells with light, using “optogenetic” stimulation upstream of Rac t o steer neutrophils .
Before diving deeper, here’s what you’ll see:
Left = experiment, right = simulation.
Green = cell edge, blue = light stimulus.

Previous models of cell polarity capture basic movements, but not flexibility. When the chemical signal changes direction, they stay locked in place. Our revised model (right) reorients and tracks the new direction. We’re releasing the full story today as a preprint – link below.

A cell navigating a chemical gradient is like being blindfolded in a dense forest, trying to find a clearing by feeling slight changes in the breeze. No map, no clear path. And yet, immune cells can find their way. I build models to understand how.

Morpheus Multicellular Simulation

If any of this interests you, I invite you to visit Morpheus's home page: morpheus.gitlab.io and feel free to contact me at jupitera@math.ubc.ca.

Here’s a short video of one of my simulated cells responding to optogenetic inputs: the green shows Rac concentration on the cell edge, and the blue dashed circles indicate the regions of optogenetic stimulation, mimicking their experimental setup.

This project involves crafting intricate PDEs and implementing them in Morpheus to test and elaborate on what they’ve observed in the lab.

My role has been to model their cells and demonstrate how incorporating this hypothesis enhances the ability of virtual cells to realign their fronts during chemotaxis. Additionally, I’ve been working to explain Jason’s most surprising results.

In 2023, Jason published a paper presenting compelling evidence for a local inhibitor of Rac within its downstream effects, along with extensive data and some unexpected results from different light stimulation configurations.

Most recently, I have been collaborating with Dr. Orion Weiner and Dr. Jason Town to model HL-60 neutrophil-like cells modified to respond to optogenetic stimulation.

Soon you’ll be able to read about it in a review paper I co-authored with Dr. Leah Keshet, Jack M. Hughes, and Ali Fele-Paranj. The paper has been accepted and will be featured in the next Cold Spring Harbor Perspectives volume on Cell Migration. Here’s a video of the project in action:

This project was particularly refined as it incorporated two stages of cellular differentiation, governed by internal gene expressions, and cell sorting driven by differential cell-cell adhesion forces.

Another interesting project I developed in Morpheus over the years was a simulation of mammalian embryo development, starting from a single zygote cell and progressing to the 128-cell stage.

I highly recommend trying out this tool and following along with the tutorial. By the end, you should be able to craft simulations like this one where I have two cells that follow a chemical gradient through chemotaxis:

YouTube video by Jupiter Algorta Morpheus Tutorial - Part 1 Description, Space, and Time

I demonstrate this in the video tutorials I created a few years ago, which you can find here (though I still need to complete Part 3, it provides a great starting point): www.youtube.com/watch?v=DLNj.... Yes, I know… I had my head shaved at the time, and it looks a bit weird!

The software features a user-friendly graphical interface, where users can simply drag and drop elements to build and customize their virtual cellular environments.

In 2014, a group at TU Dresden—Jörn Starruß, Walter de Back, Lutz Brusch, and Andreas Deutsch—created Morpheus, a software designed to allow users to implement their models with little to no programming knowledge.

Over the years, CPM has evolved to include increasingly complex descriptions and fascinating dynamics, making it an indispensable tool for exploring cellular behaviour. With its growing popularity, many software tools and packages were developed to facilitate the implementation of CPM.

CPM was revolutionary because it provided a framework to model cells as dynamic entities with defined shapes, sizes, and interactions spanning intracellular and intercellular scales, rather than treating them as points or oversimplified objects.

Morpheus utilizes the Cellular Potts Model (CPM), an extension of the Potts model developed by Dr. James A Glazier and Dr. François Graner in 1992.

Inspired by the huge community of researchers that work in cell migration I was inspired to create my BlueSky profile. For my first post here, I’d like to share a bit about my favourite cellular modelling tool, Morpheus, and share some of my fun simulations with a small tutorial I’ve done for it.