Calin Plesa
@calin.bsky.social
Assistant Prof. @uoknightcampus.bsky.social. Cofounder @synplexity.bsky.social. Gene synthesis, synbio, protein engineering, nanopores, multiplex assays. Opinions my own. www.plesalab.org
The BioE dept in the Knight Campus is a great place to work and is unique in many ways! We are expanding over the next few years with our second building opening in 2026. Come join us, applications begin review on October 15. ...4/n
September 9, 2025 at 5:38 PM
The BioE dept in the Knight Campus is a great place to work and is unique in many ways! We are expanding over the next few years with our second building opening in 2026. Come join us, applications begin review on October 15. ...4/n
Computational & Data-Science Neuroengineering: neural signal processing and analytics, closed-loop behavior tracking, neuromorphic computing and brain-inspired AI, spatial multi-omics analysis ...3/n
September 9, 2025 at 5:35 PM
Computational & Data-Science Neuroengineering: neural signal processing and analytics, closed-loop behavior tracking, neuromorphic computing and brain-inspired AI, spatial multi-omics analysis ...3/n
Experimental & Translational Neuroengineering: neural interfaces, neurophotonics for brain stimulation/recording/imaging, pre-clinical bioelectric medicine or brain injury repair models, brain organoid technology, disease models ...2/n
September 9, 2025 at 5:34 PM
Experimental & Translational Neuroengineering: neural interfaces, neurophotonics for brain stimulation/recording/imaging, pre-clinical bioelectric medicine or brain injury repair models, brain organoid technology, disease models ...2/n
We’d love to hear your comments and feedback! Disclosure: I’m a co-founder and equity holder in @synplexity.bsky.social, which is commercializing DropSynth to empower other researchers to perform similar studies at scale. 13/n
January 28, 2025 at 1:45 AM
We’d love to hear your comments and feedback! Disclosure: I’m a co-founder and equity holder in @synplexity.bsky.social, which is commercializing DropSynth to empower other researchers to perform similar studies at scale. 13/n
Computational: There is a huge amount of data here and we have only started scratching the surface in its analysis. We’ve already started playing around with ML models for prediction and generation. 12/n
January 28, 2025 at 1:44 AM
Computational: There is a huge amount of data here and we have only started scratching the surface in its analysis. We’ve already started playing around with ML models for prediction and generation. 12/n
Experimental: this study was only an initial pilot. We’re assembling a library 10x as large and with continuing improvements in NGS, the amount of functional data that can be collected will be incredible. 11/n
January 28, 2025 at 1:43 AM
Experimental: this study was only an initial pilot. We’re assembling a library 10x as large and with continuing improvements in NGS, the amount of functional data that can be collected will be incredible. 11/n
There is a lot more discussed in the preprint, but I’ll wrap up with some thoughts about the future. 10/n
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Exploring Antibiotic Resistance in Diverse Homologs of the Dihydrofolate Reductase Protein Family through Broad Mutational Scanning
Current antibiotic resistance studies often focus on individual protein variants, neglecting broader protein family dynamics. Dihydrofolate reductase (DHFR), a key antibiotic target, has been extensiv...
www.biorxiv.org
January 28, 2025 at 1:42 AM
There is a lot more discussed in the preprint, but I’ll wrap up with some thoughts about the future. 10/n
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Zooming in: Each homolog typically has ~30 mutants. This granular view lets us see not just overall trends but also some of the individual mutations driving resistance or loss of function. 9/n
January 28, 2025 at 1:42 AM
Zooming in: Each homolog typically has ~30 mutants. This granular view lets us see not just overall trends but also some of the individual mutations driving resistance or loss of function. 9/n
Next, we turned to Trimethoprim resistance. We examined how each homolog behaved across 6 concentrations, with only a few still surviving at the highest concentration tested. 8/n
January 28, 2025 at 1:41 AM
Next, we turned to Trimethoprim resistance. We examined how each homolog behaved across 6 concentrations, with only a few still surviving at the highest concentration tested. 8/n
Patterns in gain-of-function mutants pointed to specific regions critical for restoring function. In DHFR many factors contribute to fitness: catalytic activity, expression level, folding, metabolic flux, coupling to thymidylate synthase, PPIs, … 7/n
January 28, 2025 at 1:39 AM
Patterns in gain-of-function mutants pointed to specific regions critical for restoring function. In DHFR many factors contribute to fitness: catalytic activity, expression level, folding, metabolic flux, coupling to thymidylate synthase, PPIs, … 7/n
The silver lining: gain-of-function mutants. Many poorly complementing homologs gained function with minor changes. Including mutants up to 3 a.a. away increases the fraction of complementing homologs to 91%. 6/n
January 28, 2025 at 1:38 AM
The silver lining: gain-of-function mutants. Many poorly complementing homologs gained function with minor changes. Including mutants up to 3 a.a. away increases the fraction of complementing homologs to 91%. 6/n