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Posts by Michalis Averof

Very nice work! I guess what we call 'initial conditions' depends on how we define the mechanisms that we focus on. In reality it is a continuous series of integrated events from egg to fish, no?

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I almost forgot: a big thank you to Development's @dev-journal.bsky.social editorial and production teams for being supportive, flexible and responsive re: editorial communication and deadlines, during a period when I faced a serious health problem. It means a lot to have this support.

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Many more colleagues are playing with this toolkit in different species. I'll be excited to see the results coming from amphioxus, snails, ctenophores, sponges, various unicellular eukaryotes, brown algae... 9/9

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I am grateful to all our co-authors in this exciting collaboration. And grateful to our funding agencies, who keep supporting blue skies research – in our case ANR @agencerecherche.bsky.social 🙏

Most of the work was done in Europe and supported by national funding agencies 8/9

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The paper we just published is a collaboration of 12 labs spread across 7 countries, covering sea squirt (shown here), sea urchin, beetle, crustacean, roundworm, ragworm, flatworm, jellyfish, sea anemone & choanoflagellate. Comparing the results identified tags that work well across many species 7/9

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Irene's first tests looked promising, so we started sharing our toolkit with colleagues who could try it in a wide range of species. The wider the better. We advertised on social media, sent to @addgene.bsky.social, and shared these strips through the post and at meetings. It was great fun. 6/9

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Our colleague Mette had already sent me a few tags, but we wanted to try more. We searched papers, discussed with colleagues and came up with 11 candidates, targeting the membrane by different routes. We prepared them in a way that would be easy to apply in different species (by injecting mRNA). 5/9

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Two years ago, Irene Karapidaki and I were looking for tags we could use in the crustacean Parhyale, to study how they regenerate their legs after injury. We had movies of regenerating legs where cell nuclei are visible (using nucleus-localising tags) but the shapes of cells were invisible. 4/9

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Several membrane-localising tags have been described in well-studied 'model' organisms, but these do not always work well in other species. Here is an example in crustacean embryos: on the left is a tag that works well, on the right is one that gets stuck inside the cell. 3/9

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Targeting the cell membrane in established and emerging model organisms Summary: Screening a toolkit of diverse membrane-localising tags identifies candidates that efficiently localise proteins to the plasma membrane in a wide range of animals and choanoflagellates.

Finding molecular tags that localise fluorescent proteins to the cell membrane was the goal of our latest paper, now published in Development @dev-journal.bsky.social. The tags act as address labels, sending proteins to the cell membrane, where they highlight the shape and arrangement of cells. 2/9

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These images show live embryos of animals (jellyfish, crustacean, worm, sea urchin, sea squirt, beetle) and one of animals closest single-celled relatives. They were captured taking advantage of fluorescent proteins localised on the outer membrane of cells, allowing us to observe cell outlines. 1/9

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It's the field work and the discovery I enjoy. I can't say I'm fascinated by taxonomy per se. Thankfully I have expert colleagues.

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I am thankful for all the fun and good luck in finding these species. Special thanks to Farzaneh, Sabrina, Chryssa and Olli, and to long-time collaborator and genomics master Mathilde.

Our next frontier: high quality sequencing and assembly of P. plumicornis genome by @atlasea.bsky.social

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We found something that looked like aquilina, but identification of this species is tough and only reliable in males. We collected aquilina-like males and the females they coupled with, hoping for the best. Genome sequencing later confirmed that we had the right species. /8

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Later, in September 2023 I spent a month in the north of Greece, with my daughter Marta who was doing anthropology fieldwork in the Pomak villages above Xanthi. I met Chryssa Anastasiadou at a fisheries institute near Kavala and we went collecting in the area, with her colleague Pavlos Vidoris. /7

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Parhyale plumicornis was there, right under my nose! Over a week I collected from the rocky shores ~20 individuals. They travelled well back to Lyon and started a culture that's still running after 3.5 years. /6

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A few months later I was on holidays in Milos, in the Cyclades, a place I visit almost every summer in the last 25 years. I brought a portable stereoscope and collected some amphipods a few hundred metres from where we lived. /5

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In May 2022 we met Oliver Coleman at the Natural History Museum of Berlin, just a few months before he retired. The museum collections are quite poor on Parhyale, but meeting Olli was great! /4

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We searched along the rocky coast for 3 days; we could only find 3 individuals /3

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Farzaneh sent us some Parhyale darvishi, preserved in ethanol. Sabrina offered to help us collect Parhyale plumicornis in Sicily.

In April 2022 Mathilde and I travelled to Sicily; we set up a basic lab in a flat in Trapani, with a stereoscope from Palermo /2

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Οur recent preprint includes data from 3 new Parhyale species: aquilina & plumicornis from the Mediterranean, darvishi from the Persian Gulf

I started looking for such species in 2021. Amphipod expert Oliver Coleman gave me some key contacts: Farzaneh Momtazi (Iran) & Sabrina Lo Brutto (Palermo) /1

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you're too kind, but “it’s not where you take ideas from, it’s where you take them to” (Jean-Luc Godard)
;)

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Do you work with a strange model species and are frustrated by the lack of antibodies for immunos? Here's a web app that does some computational pre-screening for you.
sixpack-abscan.serve.scilifelab.se

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NB. Data should be released in the coming week

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Credit to all co-authors for a great collaboration. Gillian Forbes, Emilia Skafida, Irene Karapidaki developed the approach and generated resources. Mathilde Paris led the omics and data crunching. Thanks to @frm-officiel.bsky.social @erc.europa.eu @ec.europa.eu for supporting our research. /5

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Producing these resources might seem costly, but we found we could detect islands of sequence conservation with low coverage genome sequencing (~10X), by mapping sequence reads across species (no need assemble the genomes). Saves a lot of money and effort, particularly on large genomes. /4

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These approaches allow us to narrow down the search for cis-reg elements and to search genome-wide for elements with particular properties. This has allowed us to identify ubiquitous, muscle- and neuron-specific cis elements, driving robust expression of transgenic reporter constructs. /3

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We combined 2 approaches to identify cis-reg elements. First, we produced bulk & single nucleus ATACseq data, to focus on sequences that are accessible for gene regulation. Second, we sequenced the genomes of 3 additional Parhyale spp, to identify islands of seq conservation across the genome. /2

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In animals with large genomes, finding cis-regulatory elements can be very challenging. Enhancers can be located tens/hundreds of kb away from their target promoters. We face this challenge in Parhyale, with >3 Gbp genome.
We just published a preprint describing how we are tackling this problem. /1

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I like this concept of the genome as a compressed representation of an organism. Not like a ZIP file that recreates the same file in smaller form, but more like an AI model where a compact sequence (DNA) generates an organism through probabilistic interactions using molecules that it encodes itself.

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