Cameron Dale MacQuarrie

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zoogle.arcadiascience.com told us Chlamy is a great model for ADA1 — so we tried it!

Come chat about it:
Sunday Dec 7, 2:15–3:45 pm (digital poster, near the @ascbiology.bsky.social booth)
Monday Dec 8, 2:15–3:45 pm (paper poster, B538)

Excited to share some new work from @arcadiascience.com at #CellBio2025!

We’re using Chlamydomonas reinhardtii as a rapid in vivo platform to model ADA1 deficiency and test computationally designed therapeutic ADA1 variants.

Poster PDF: bit.ly/chlamy-ADA

This work highlights why genetic background matters in model organisms! Even after multiple rounds of backcrossing, unexpected phenotypes can emerge that may not be directly related to the gene you're studying. @ArcadiaScience [9/9]

To figure this out, we're testing another CPC1 mutant (cpc1-2) from a different genetic background and trying to rescue both with wild-type CPC1 expression. This should tell us if these growth phenotypes are due to the mutation or genetic background. [8/9]

Why does cpc1-1 behave so differently? It might be retaining genetic material from its parent strain despite backcrossing. Or maybe the CPC1 protein itself plays a role in metabolism - it does interact with enolase and other glycolytic enzymes! [7/9]

Third, after 47 days, cpc1-1 was the ONLY strain that could grow on marine medium with high salt content, revealing an unexpected halotolerance. [6/9]

Second, on nitrate-containing media, wild-type C. reinhardtii and ida4 showed chlorosis (yellowing) as expected due to their nit2 mutation. But cpc1-1 maintained dark green colonies, suggesting it can use nitrate efficiently. [5/9]

First, cpc1-1 showed enhanced growth on media with proteose peptone, outperforming wild-type strains that barely grew in this condition! [4/9]

The cpc1-1 mutant (which has defects in the central pair complex of flagella) showed three surprising growth phenotypes that weren't present in other strains, including the ida4 mutant (which has inner dynein arm defects). [3/9]

We were studying flagellar mutants as models for human ciliary diseases when we noticed something odd about their growth patterns. So we decided to compare growth across different media types to see if these mutations affect metabolism beyond just flagellar function. [2/9]

Discovered some unexpected growth phenotypes in Chlamydomonas flagellar mutants! The cpc1-1 strain (with central pair complex defects) shows surprising metabolic traits that might be independent of its flagellar defects. 🧵 research.arcadiascience.com/pub/observat... [1/9]

Happy Darwin Day! Today, we’re thinking about how to use evolution to accelerate biomedical research. We think the answer is to expand the repertoire of organismal models. Search for the best ones using our new portal, Zoogle: zoogle.arcadiascience.com 🧵

Today at #CellBio24, I'll discuss our new pub at the "Quantitative Biology in Emerging Model Systems" subgroup session at 5:15 pm in Ballroom 20A. Come check it out!

Today at #CellBio24, Dave Mets will be at poster B599 talking about mapping genotypes to phenotypes!

poster: zenodo.org/records/1449...

Our new pub dropped this weekend!

For those at #CellBio24, I'll be at poster B73 starting at 11:15 am discussing this work!

I'll also be giving a talk on Tuesday at 5:15 pm in Ballroom 20A in the Quantitative Biology in Emerging Model Systems session

poster here: zenodo.org/records/14481493

Rescuing Chlamydomonas motility in mutants modeling spermatogenic failure We used Chlamydomonas reinhardtii motility mutants with disrupted genes homologous to human SPEF2 or DNALI1 to model spermatogenic failure disorders SPGF43 and SPGF83, respectively. We recovered aspec...

Thanks to the team at @arcadiascience.bsky.social! Especially @taraeb.bsky.social, Ryan Lane, Dave Mets, @meganhoch.bsky.social, & Audrey Bell who made this work possible! Check out the pub here (research.arcadiascience.com/pub/result-chlamy-spgf) & feel free to comment! We love feedback! [8/8]

GitHub - Arcadia-Science/2024-chlamy-mutant-motility-pub at v1.0 Collection of data, code, scripts, and notebooks accompanying the pub "Rescuing Chlamydomonas Motility in Mutants Modeling Spermatogenic Failure." - GitHub - Arcadia-Science/2024-chlamy-m...

While this project is now on ice (explained in pub), all code & data are available: 🔗 GitHub: (github.com/Arcadia-Scie...) 📊 BioImage Archive: (www.ebi.ac.uk/biostudies/b...). [7/8]

The different effects of each drug highlight how similar swimming problems can arise from distinct molecular pathways. What works for one genetic variant may not work for another [6/8]

Despite similar motility defects, the mutations responded differently to treatment —- what rescued one mutation often had no effect on the other. This suggests mutation-specific therapeutic approaches are needed [5/8]

We developed two complementary approaches to measure motility: a population "sink-or-swim" assay and detailed single-cell tracking with SwimTracker (research.arcadiascience.com/pub/resource-swimtracker-htp-swimming-assay/release/2). This revealed how drugs affect different aspects of swimming [4/8]

These mutants were characterized decades ago and show similar swimming defects to those seen in SPGF patients' sperm. Our phylogenetic framework showed they're excellent models for SPGF83 and SPGF43 [3/8]

We used phylogenetic analysis from our pub led by Ryan York, Austin Patton & @pracheeac.bsky.social (research.arcadiascience.com/pub/result-evolutionary-organismal-selection) and found Chlamydomonas proteins have high conservation with SPGF proteins. [2/8]

Rescuing Chlamydomonas motility in mutants modeling spermatogenic failure We used Chlamydomonas reinhardtii motility mutants with disrupted genes homologous to human SPEF2 or DNALI1 to model spermatogenic failure disorders SPGF43 and SPGF83, respectively. We recovered aspec...

🧵 New from @arcadiascience.bsky.social: We used Chlamydomonas mutants to model specific types of spermatogenic failure and found drugs can rescue swimming behavior in mutation-specific ways. Full pub: research.arcadiascience.com/pub/result-chlamy-spgf [1/8]

Tomorrow at #CellBio24, I'll be at poster (B73) talking about some fun new work we just released using Chlamydomonas to model spermatogenic failure.

Check out the poster here: zenodo.org/records/14481493

Join the fun and post your comments & questions on the pub!
bit.ly/chlamy-spgf

Happening soon at #CellBio24 @ascbiology.bsky.social

Ryan York's poster (B574) on a data-driven approach to selecting your model organism @arcadiascience.bsky.social

Poster here: zenodo.org/records/14479386

Join the fun & post your comments & questions on the pub!
bit.ly/evolutionary...

Ryan’s poster:
zenodo.org/doi/10.5281/...

The concept:
research.arcadiascience.com/pub/idea-sel...

The approach and analyses:
research.arcadiascience.com/pub/result-e...

The validation:
research.arcadiascience.com/pub/result-c...

If you’re at #CellBio2024 drop by Ryan’s poster today (Board B574) to hear the latest from @arcadiascience.bsky.social about how you can choose the right model system for your research or find areas best studied in the species you have expertise/infrastructure
Poster and publications below

PhyloPic PhyloPic is an open database of free silhouette images of animals, plants, and other life forms, available for reuse under Creative Commons licenses. Download silhouettes for use in educational materi...

Annual reminder that PhyloPic is your free go-to source for organismal silhouettes for #Jack-o'-lantern designs phylopic.org @tmkeesey.bsky.social 🧪

Phenotypic differences between interfertile Chlamydomonas species · Genetics: Decoding evolutionary... We’re crossing C. reinhardtii and C. smithii algae for high-throughput genotype-phenotype mapping. In preparation, we’re comparing the parents to uncover unique species-specific phenotypes.

Find all of our findings, code, and data at research.arcadiascience.com/pub/result-c...

We’re eager to get your feedback on this work! Please post any thoughts, questions, or concerns on our pub!