Manuel Irimia
@mirimiam.bsky.social
ICREA Evolutionary Biologist working on transcriptomics of development and evolution at @upf.edu and @crg.eu. Coordinator of the @evomg-bcn.bsky.social Joint Program.
Lab website: http://transdevolab.com
Lab website: http://transdevolab.com
The second project will investigate the evolution of bat pancreases at the single-cell level to identify transcriptomic adaptations to dietary shifts. The ultimate goal is to find genomic changes that could shed light into type 2 diabetes risk in humans.
www.evomg-dn.eu/project/mole...
www.evomg-dn.eu/project/mole...
October 15, 2025 at 7:02 AM
The second project will investigate the evolution of bat pancreases at the single-cell level to identify transcriptomic adaptations to dietary shifts. The ultimate goal is to find genomic changes that could shed light into type 2 diabetes risk in humans.
www.evomg-dn.eu/project/mole...
www.evomg-dn.eu/project/mole...
The first project aims to identify transcriptomic susceptibilities (in gene expression and alternative #splicing) to cancer across mammals to explain differences in cancer prevalence. We will also investigate cancer type evolution under this transcriptomic prism.
www.evomg-dn.eu/project/evol...
www.evomg-dn.eu/project/evol...
October 15, 2025 at 7:02 AM
The first project aims to identify transcriptomic susceptibilities (in gene expression and alternative #splicing) to cancer across mammals to explain differences in cancer prevalence. We will also investigate cancer type evolution under this transcriptomic prism.
www.evomg-dn.eu/project/evol...
www.evomg-dn.eu/project/evol...
🚨🚨🚨 New review article on #microexons from the lab! A comprehensive recap of the current state of the field by @tahneema.bsky.social.
www.annualreviews.org/content/jour...
www.annualreviews.org/content/jour...
September 1, 2025 at 10:20 AM
🚨🚨🚨 New review article on #microexons from the lab! A comprehensive recap of the current state of the field by @tahneema.bsky.social.
www.annualreviews.org/content/jour...
www.annualreviews.org/content/jour...
🧬🧬🧬 New review from the lab:
Evolution of comparative transcriptomics: biological scales, phylogenetic spans, and modeling frameworks
authors.elsevier.com/sd/article/S...
By @mattezambon.bsky.social & @fedemantica.bsky.social, together with @jonnyfrazer.bsky.social & Mafalda Dias.
Evolution of comparative transcriptomics: biological scales, phylogenetic spans, and modeling frameworks
authors.elsevier.com/sd/article/S...
By @mattezambon.bsky.social & @fedemantica.bsky.social, together with @jonnyfrazer.bsky.social & Mafalda Dias.
August 6, 2025 at 9:16 AM
🧬🧬🧬 New review from the lab:
Evolution of comparative transcriptomics: biological scales, phylogenetic spans, and modeling frameworks
authors.elsevier.com/sd/article/S...
By @mattezambon.bsky.social & @fedemantica.bsky.social, together with @jonnyfrazer.bsky.social & Mafalda Dias.
Evolution of comparative transcriptomics: biological scales, phylogenetic spans, and modeling frameworks
authors.elsevier.com/sd/article/S...
By @mattezambon.bsky.social & @fedemantica.bsky.social, together with @jonnyfrazer.bsky.social & Mafalda Dias.
📉 cAMP-targeting pharmacological treatments also mimic and reverse srrm3-dependent transcriptional signatures, including immediate early gene downregulation. Combined with persistent AP1/CREB motif occupancy, it all suggests a longer-term adaptation to sustained neuronal hyperactivity. 9/9
April 28, 2025 at 9:24 AM
📉 cAMP-targeting pharmacological treatments also mimic and reverse srrm3-dependent transcriptional signatures, including immediate early gene downregulation. Combined with persistent AP1/CREB motif occupancy, it all suggests a longer-term adaptation to sustained neuronal hyperactivity. 9/9
⚙️ But what underlies the hyperarousal at the molecular level? Behavioral pharmacology pointed us to elevated cAMP signaling as the likely driver!
● Inhibiting adenylyl cyclases (reducing cAMP) rescued mutant hyperactivity.
● Increasing cAMP in the wild-type phenocopied the mutant.
8/9
● Inhibiting adenylyl cyclases (reducing cAMP) rescued mutant hyperactivity.
● Increasing cAMP in the wild-type phenocopied the mutant.
8/9
April 28, 2025 at 9:24 AM
⚙️ But what underlies the hyperarousal at the molecular level? Behavioral pharmacology pointed us to elevated cAMP signaling as the likely driver!
● Inhibiting adenylyl cyclases (reducing cAMP) rescued mutant hyperactivity.
● Increasing cAMP in the wild-type phenocopied the mutant.
8/9
● Inhibiting adenylyl cyclases (reducing cAMP) rescued mutant hyperactivity.
● Increasing cAMP in the wild-type phenocopied the mutant.
8/9
🧬 RNA-seq of FACS-sorted neurons revealed large-scale mis-splicing of conserved neural microexons. Interestingly, many microexon-harboring genes, for example involved in calcium ion homeostasis or synapse organization, were upregulated, suggesting a compensatory response to mis-splicing. 7/9
April 28, 2025 at 9:24 AM
🧬 RNA-seq of FACS-sorted neurons revealed large-scale mis-splicing of conserved neural microexons. Interestingly, many microexon-harboring genes, for example involved in calcium ion homeostasis or synapse organization, were upregulated, suggesting a compensatory response to mis-splicing. 7/9
🧠 Zooming into the brain with 2P calcium imaging: srrm3∆eMIC mutant neurons were hyperactive, and forebrain activity remained elevated even during stress-inducing visual stimuli - despite reduced visually-evoked responses (due to known photoreceptor loss). 6/9
April 28, 2025 at 9:24 AM
🧠 Zooming into the brain with 2P calcium imaging: srrm3∆eMIC mutant neurons were hyperactive, and forebrain activity remained elevated even during stress-inducing visual stimuli - despite reduced visually-evoked responses (due to known photoreceptor loss). 6/9
🐟 Using high-speed tracking, we found that srrm3∆eMIC larvae more frequently engage in high-displacement, stress-associated swims - even without any stimulus. They also showed seizure-like episodes: prolonged, atypical swim bouts with hyperkinetic features. 5/9
April 28, 2025 at 9:24 AM
🐟 Using high-speed tracking, we found that srrm3∆eMIC larvae more frequently engage in high-displacement, stress-associated swims - even without any stimulus. They also showed seizure-like episodes: prolonged, atypical swim bouts with hyperkinetic features. 5/9
💥 We studied zebrafish mutants lacking the srrm3 eMIC domain (essential for microexon inclusion). These srrm3∆eMIC larvae showed: hyperlocomotion, severe sleep loss, anxiety-like behaviours and sensory hypersensitivity - all pointing to hyper-arousal! 4/9
April 28, 2025 at 9:24 AM
💥 We studied zebrafish mutants lacking the srrm3 eMIC domain (essential for microexon inclusion). These srrm3∆eMIC larvae showed: hyperlocomotion, severe sleep loss, anxiety-like behaviours and sensory hypersensitivity - all pointing to hyper-arousal! 4/9
However, systematically assessing these two functional fates is tricky, as the functional readout depends on the nature of each protein (e.g. ion channels, TFs, etc). Check out the final sections to see why we think functional specialization might be dominant, and for ideas about future studies. 7/7
March 18, 2025 at 1:53 PM
However, systematically assessing these two functional fates is tricky, as the functional readout depends on the nature of each protein (e.g. ion channels, TFs, etc). Check out the final sections to see why we think functional specialization might be dominant, and for ideas about future studies. 7/7
Importantly, even if highly associated, expression and functional fates do not have a 1:1 correspondence. Expression specialization enables conservation of the ancestral function and promotes cell-type evolution both in case of functional specialization and neofunctionalization. 6/7
March 18, 2025 at 1:53 PM
Importantly, even if highly associated, expression and functional fates do not have a 1:1 correspondence. Expression specialization enables conservation of the ancestral function and promotes cell-type evolution both in case of functional specialization and neofunctionalization. 6/7
By re-analyzing published data under this framework, we showed that expression specialization is the prevalent fate following gene duplication in several scenarios. Moreover, we suggest it might be prevalent for alternative isoforms as well! 5/7
March 18, 2025 at 1:53 PM
By re-analyzing published data under this framework, we showed that expression specialization is the prevalent fate following gene duplication in several scenarios. Moreover, we suggest it might be prevalent for alternative isoforms as well! 5/7
We classified all such fates, introducing the concept of expression specialization (i.e., restriction of the ancestral expression) and functional specialization (i.e., optimation of the original function) for one paralogous gene or alternative isoform in few tissues/cell-types. 4/7
March 18, 2025 at 1:53 PM
We classified all such fates, introducing the concept of expression specialization (i.e., restriction of the ancestral expression) and functional specialization (i.e., optimation of the original function) for one paralogous gene or alternative isoform in few tissues/cell-types. 4/7
Gene duplication (GD) and alternative splicing (AS) provide an elegant solution: they expand the ancestral protein repertoire by generating paralogous genes and alternative isoforms, which can undergo various expressions and functional fates with distinct evolutionary outcomes. 3/7
March 18, 2025 at 1:53 PM
Gene duplication (GD) and alternative splicing (AS) provide an elegant solution: they expand the ancestral protein repertoire by generating paralogous genes and alternative isoforms, which can undergo various expressions and functional fates with distinct evolutionary outcomes. 3/7
The problem is “simple”: highly conserved and presumably ancestrally ubiquitous genes are prevalent in extant animal genomes. However, how can these genes contribute to the evolution of tissue/cell-types specific traits while preserving their original widespread function? 2/7
March 18, 2025 at 1:53 PM
The problem is “simple”: highly conserved and presumably ancestrally ubiquitous genes are prevalent in extant animal genomes. However, how can these genes contribute to the evolution of tissue/cell-types specific traits while preserving their original widespread function? 2/7
"The main fates after gene duplication are gene loss, redundancy, subfunctionalization and neofunctionalization".
In our new review, @fedemantica.bsky.social and I argue we are missing the most prevalent one: specialization. And the same applies to alternative splicing! 1/7
tinyurl.com/45k7kbmp
In our new review, @fedemantica.bsky.social and I argue we are missing the most prevalent one: specialization. And the same applies to alternative splicing! 1/7
tinyurl.com/45k7kbmp
March 18, 2025 at 1:53 PM
"The main fates after gene duplication are gene loss, redundancy, subfunctionalization and neofunctionalization".
In our new review, @fedemantica.bsky.social and I argue we are missing the most prevalent one: specialization. And the same applies to alternative splicing! 1/7
tinyurl.com/45k7kbmp
In our new review, @fedemantica.bsky.social and I argue we are missing the most prevalent one: specialization. And the same applies to alternative splicing! 1/7
tinyurl.com/45k7kbmp
Finally, transcriptomic comparisons between mutant larvae and their wild type siblings suggest that coordinated misregulation of specific neural-related pathways may provide functional compensations at the molecular level. 8/9
December 30, 2024 at 4:07 PM
Finally, transcriptomic comparisons between mutant larvae and their wild type siblings suggest that coordinated misregulation of specific neural-related pathways may provide functional compensations at the molecular level. 8/9
We also implemented a new method for primary neuronal culture and neurite length quantification from FACSorted HuC+ neurons. With this method we also identified microexons whose deletion leads to decreased (vav2) or increased (evi5b, itsn1) neurite lengths. 7/9
December 30, 2024 at 4:07 PM
We also implemented a new method for primary neuronal culture and neurite length quantification from FACSorted HuC+ neurons. With this method we also identified microexons whose deletion leads to decreased (vav2) or increased (evi5b, itsn1) neurite lengths. 7/9
In contrast to the strong phenotypes observed for their master regulator srrm3, most microexon mutants showed no phenotypes for most tests, with a few notable exceptions. For instance, vti1 and kif1b KOs showed social defects, yet far from those of the srrm3 mutant (blind) fish. 6/9
December 30, 2024 at 4:07 PM
In contrast to the strong phenotypes observed for their master regulator srrm3, most microexon mutants showed no phenotypes for most tests, with a few notable exceptions. For instance, vti1 and kif1b KOs showed social defects, yet far from those of the srrm3 mutant (blind) fish. 6/9
To tackle this major open question, common to other tissue-specific splicing regulators, we generated CRISPR-Cas9 deletion mutants in zebrafish for 18 conserved neural-specific microexons regulated by srrm3/4, as well for srrm3 and srrm4. 4/9
December 30, 2024 at 4:07 PM
To tackle this major open question, common to other tissue-specific splicing regulators, we generated CRISPR-Cas9 deletion mutants in zebrafish for 18 conserved neural-specific microexons regulated by srrm3/4, as well for srrm3 and srrm4. 4/9
Microexons display striking conservation and switch-like regulation in neurons by the splicing factors Srrm3 and Srrm4. Consequently, disruption of these regulators leads to severe neurological phenotypes in mice, and their misregulation is linked to human disease. 2/9
December 30, 2024 at 4:07 PM
Microexons display striking conservation and switch-like regulation in neurons by the splicing factors Srrm3 and Srrm4. Consequently, disruption of these regulators leads to severe neurological phenotypes in mice, and their misregulation is linked to human disease. 2/9
🚨🚨🚨
If you're a bioinformatician who loves:
🧬 #SingleCell #LongReadSequencing & #AlternativeSplicing
🚀 Collaborating and travelling
Apply to work with us at the spectacular BIMSB (@mdc-berlin.bsky.social) in Berlin + @upf.edu-@crg.eu in Barcelona. Qs: www.transdevolab.com
Please RT! 🙏
If you're a bioinformatician who loves:
🧬 #SingleCell #LongReadSequencing & #AlternativeSplicing
🚀 Collaborating and travelling
Apply to work with us at the spectacular BIMSB (@mdc-berlin.bsky.social) in Berlin + @upf.edu-@crg.eu in Barcelona. Qs: www.transdevolab.com
Please RT! 🙏
December 23, 2024 at 3:54 PM
🚨🚨🚨
If you're a bioinformatician who loves:
🧬 #SingleCell #LongReadSequencing & #AlternativeSplicing
🚀 Collaborating and travelling
Apply to work with us at the spectacular BIMSB (@mdc-berlin.bsky.social) in Berlin + @upf.edu-@crg.eu in Barcelona. Qs: www.transdevolab.com
Please RT! 🙏
If you're a bioinformatician who loves:
🧬 #SingleCell #LongReadSequencing & #AlternativeSplicing
🚀 Collaborating and travelling
Apply to work with us at the spectacular BIMSB (@mdc-berlin.bsky.social) in Berlin + @upf.edu-@crg.eu in Barcelona. Qs: www.transdevolab.com
Please RT! 🙏
We’re recruiting a PhD student to use comparative omics to investigate why some viruses can efficiently infect both human and mosquito cells, but lead to different infection outcomes. Fully funded position by @evomg-bcn.bsky.social at our lab at UPF-CRG and the Diez lab.
www.crg.eu/en/content/t...
www.crg.eu/en/content/t...
December 10, 2024 at 11:33 AM
We’re recruiting a PhD student to use comparative omics to investigate why some viruses can efficiently infect both human and mosquito cells, but lead to different infection outcomes. Fully funded position by @evomg-bcn.bsky.social at our lab at UPF-CRG and the Diez lab.
www.crg.eu/en/content/t...
www.crg.eu/en/content/t...