Bioinf-l

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bioinf-l@kam.mff.cuni.cz

November 2024

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Lecture invitation: Gene Off, Insights On: Mapping Molecular Phenotypes with MorPhiC
by Petr Danecek 26 Nov '24

26 Nov '24

Dear all, the next seminar will take place on Wednesday, please see the details below. We look forward to seeing you all! Title: Gene Off, Insights On: Mapping Molecular Phenotypes with MorPhiC Speaker: Anu Shivalikanjli (EBI) Date and time: Wednesday 27/11/2024 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S3 (3rd floor) https://bioinformatics.cuni.cz/seminar/ Best wishes, Petr Danecek ------------------------------- *Anu Shivalikanjli* */Gene Off, Insights On: Mapping Molecular Phenotypes with MorPhiC / *We explore the molecular characteristics of cells that carry “null alleles” in protein-coding genes, resulting in a diminished production of their corresponding proteins. Using human induced pluripotent stem cells (iPSCs), which may change into numerous cell types, we study how these inactive genes affect cellular functions across the cell types. With precise gene-editing techniques, we can selectively deactivate genes and subsequently analyze the resulting changes using advanced methodologies such as RNA sequencing, multi-omics, and imaging. These approaches combined help us understand each gene's role and the consequences of their inactivity. Our ultimate goal is to use these models to map the effects of “null alleles” throughout the human genome. Central to this effort is the MorPhiC project, a collaborative initiative that unites multiple research centers to study “null alleles” in lab-grown cell systems. MorPhiC focuses on generating, organizing, and analyzing large datasets to catalog the molecular and cellular effects of gene knockouts for all human genes. This initiative provides a foothold understanding of how genes produce traits (phenotypes) as well as the connections between genes and regulatory components in biological pathways and networks, laying the way for future advances in human genome research.

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Lecture invitation: The genetic code and protein evolvability
by Petr Danecek 05 Nov '24

05 Nov '24

Dear all, the next seminar will take place tomorrow, please see the details below. We look forward to seeing you all! Title: The genetic code and protein evolvability Speaker: Hana Rozhoňová, M.Sc. Date and time: Wednesday 6/11/2024 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S3 (3rd floor) https://bioinformatics.cuni.cz/seminar/ Best wishes, Petr Danecek ------------------------ *Hana Rozhoňová* */The genetic code and protein evolvability/* The standard genetic code defines the rules of translation for nearly every life form on Earth. It also determines the amino acid changes accessible via single-nucleotide mutations, thus influencing protein evolvability—the ability of mutation to bring forth adaptive variation in protein function. One of the most striking features of the standard genetic code is its robustness to mutation, yet it remains an open question whether such robustness facilitates or frustrates protein evolvability. To answer this question, we use data from massively parallel sequence-to-function assays to construct and analyze 6 empirical adaptive landscapes under hundreds of thousands of rewired genetic codes. We find that robust genetic codes tend to enhance protein evolvability by rendering smooth adaptive landscapes with few peaks, which are readily accessible from throughout sequence space. Whereas the genetic codes that optimize evolvability depend to some extent on the detailed relationship between amino acid sequence and protein function, we also uncover general design principles for engineering nonstandard genetic codes for enhanced and diminished evolvability, which may facilitate directed protein evolution experiments and the bio-containment of synthetic organisms, respectively.

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