Soumillion Laboratory

Congratulation to Dr. Gol Mohammad Dorrazehi

Sebastian Worms — Tue, 18 Jan 2022 06:29:22 +0000

On January 17th, 2022, Dr. Dorrazehi became the newest member of our team to successfully defend his PhD thesis. His thesis title is “The catalytic activity of a DD-peptidase impairs its evolutionary conversion into a β-lactamase“, which is focused on “challenges in in-vivo directed evolution”, to build on previous works of our laboratory to probe the trade-offs between activity and evolvability of enzymes. In the thesis, he explored intra- and intergenic mechanisms to bypass fitness costs associated with activity of enzymes, e.g. he used the ability of CRISPR/Cas9 for creating genomic libraries to lower the fitness cost. The results of his thesis clearly demonstrate that fitness cost issues are multi-factorial and that an initial careful attention to every biological parameter may be crucial for the success of a directed evolution campaign, especially when dealing with potentially dangerous enzymatic activity such as a hydrolase.

We wish you all the best for the future!

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Congratulation to Dr. Jason Baby Chirakadavil

Sebastian Worms — Mon, 30 Aug 2021 13:10:00 +0000

Congratulation to Dr. Jason Chirakadavil! On August the 30th, he successfuly defended in front of a mixed remote and on-site audience. His thesis, “Deep mutational scanning of an alanine racemase from Streptococcus thermophilus” use the natural competence of Streptococcus bacteria to more efficiently probe the way enzymes evolve. Jason’s work ethic, supportive attitude and good cheers will be sorely missed. He will continue to explore gene transfer in Gram positive bacteria during a postdoc in the laboratory of Xavier Charpentier à the INSERM in Lyon, France.

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Chromosomal Libraries Chapter is out!

Gol Dorrazehi — Mon, 27 Jul 2020 10:23:19 +0000

A lot of the work we do in the laboratory is trying to find better ways to do Directed Evolution. One of the thing we believe is that expressing libraries in their native genomic context let you navigate the fitness landscape better.

If you want to find out how exactly we build those libraries, the detailed protocols we use, both in E. coli and in S. thermophilus have now been published as a book chapter by Springer Protocols.

“Dorrazehi G.M., Worms S., Chirakadavil J.B., Mignolet J., Hols P., Soumillion P. (2020) Building Scarless Gene Libraries in the Chromosome of Bacteria. In: Iranzo O., Roque A. (eds) Peptide and Protein Engineering. Springer Protocols Handbooks. Humana, New York, NY

Open access:
https://dial.uclouvain.be/pr/boreal/object/boreal:231618

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MT180 Sketchnoting

Sebastian Worms — Mon, 16 Sep 2019 14:05:27 +0000

The talented Emilie Gobbo took live sketchnote of Sebastian’s presentation for the MT180 contest. You can discover the result above.

You can find the rest of Emilie’s work on facebook and instagram.

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Congratulation to Sebastian for his three-minute thesis

Sebastian Worms — Wed, 10 Apr 2019 14:33:05 +0000

Sebastian joined the “Ma Thèse en 180 secondes“, the french version of the 3 minute thesis scientific vulgarization contest. We’re proud to announce that he was selected to represent the UCLouvain at the belgian final that will take place on 22/05 in Mons.

In addition, Sebastian also received the public’s prize for his talk called “Il y a-t-il quelqu’un pour sauver l’antibiotique” (“Is there someone to save the antibiotic?”)

Drawings by Émilie Gobbo
https://www.facebook.com/EmiG-256871674860819/

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Journal Club S01E02

Jason Chirakadavil — Mon, 04 Mar 2019 13:04:01 +0000

Preferences of DNA binding proteins for DNA Shape Beyond Sequence Motifs
– Jason Baby Chirakadavil

A graphical summary of the key points discussed in [1]

Brief:
Building on the recent line of research that DNA shape encodes specificity signals for transcription factor (TF)-DNA binding, Samee et al. developed an algorithm to identify enriched patterns of DNA shape directly from DNA shape profiles of TF-bound regions. These patterns, or ‘‘shape motifs,’’ correspond well with conventional sequence motifs, but often include additional nucleotides flanking the sequence motifs. They also show that apparent mismatches to the sequence motif can have similar shape to the shape motif and are potential targets for TF binding. While the observations still need experimental validation, the work shows that motif models that capture additional structural and biophysical aspects are necessary to understand the mechanism of TF-DNA binding.

Classically we only focus on the sequence of nucleotides in DNA when looking at DNA binding proteins. But recently the specific structure of DNA sequences have been under the focus of study. Binding sequences of DNA may have specific patterns of DNA shape features which may also play a role in binding affinities.

Conclusions

References:

1. Bruneau, B. G., Pollard, K. S., Samee, A. H., Bruneau, B. G., & Pollard, K. S. (2019). Article A De Novo Shape Motif Discovery Algorithm Reveals Preferences of Transcription Factors for DNA Shape Article A De Novo Shape Motif Discovery Algorithm Reveals Preferences of Transcription Factors for DNA Shape Beyond Sequence Motifs. Cell Systems, 1–16. https://doi.org/10.1016/j.cels.2018.12.001

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Journal Club S01E04

Sebastian Worms — Wed, 27 Feb 2019 15:44:14 +0000

In 1966, Lynn Margulis published her famous paper “On the origin of mitosing cells”. Bringing the theory of the endosymbiotic origin of organelles to the scientific community. Advance in molecular biology in the 1970’s brought evidence and the fact that mitochondria are derived from α-proteobacteria is now widely accepted. Many questions as to how endosymbiosis occured still remains. Notably the debate between late and early symbiogenesis and around the hydrogen hypothesis of Martin and Muller still rages on.

Discussion still rages on the exact way an α-proteobacteria turned into the mitochondria. The late-mitrochondria model where a complex protoeukaryote phagocyte a bacteria and the hydrogen hypothesis where symbiosis between a bacteria and a methanogenic archea occurs before internalysation are presented here. Picture from Archibald (2015).

In this context, this week we discuss an new paper by the lab of Peter G. Schultz out of Scripps. “Engineering yeast endosymbionts as a step toward the evolution of mitochondria“. What if we could recreate one of the endosymbiosis scenario in the laboratory, with easily modifiable model organisms? This is why Angad Metha et al. managed here, engineering a strain of the yeast S. cerevisiae that is reliant on endosymbiotic E. coli to produce ATP from non-fermentable substrate such as E. coli. By adding an ADP/ATP translocase, they are able to make E. coli complement a strain with a non-functional COX2 enzyme, an essential part of the respiratory electron transport chain of mitochondria.

Reading this paper was a lot of fun. It is the kind of project that seems a bit too crazy to be true at first, but apparently it worked!

Journal Club S01E03

Gol Dorrazehi — Wed, 27 Feb 2019 14:14:21 +0000

Discussion on Molecular Causes of Evolvability

An interesting review on “The causes of evolvability and their evolution”, published by Payne and Wanger (2018), is discussed. Three major categories on the research of evolvability are discussed: phenotypic heterogeneity, mutational robustness and adaptive landscape topography:

Phenotypic heterogeneity caused by non-genetic mechanisms are discussed:

Robustness against mutations is allowing phenotypes to tolerate more genetic diversification without any change in final behaviour:

The location of an individual or a population on an adaptive landscape, determine the degree of evolvability towards the highest adaptation:

Causes of evolvability highlighted here — phenotypic heterogeneity, mutational robustness and adaptive landscapes — are themselves subject to evolutionary change:

Leave your comments about molecular causes of evolvability and its impact on the traditional dogma of “Evolution”:

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The lab is at the jamboree

Sebastian Worms — Fri, 26 Oct 2018 09:38:56 +0000

Both our master students, Steve and Mathieu, are currently in Boston for the 2018 iGEM Jamboree, to present this year’s project, Bactwars, a new hope to fight pathogenic bacterias!

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2018 BSM Symposium

Sebastian Worms — Thu, 25 Oct 2018 16:46:01 +0000

The lab was present in force at the 2018 meeting of the Belgian Society of Microbiology. Jason and Gol each presented posters on their projects.

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