Evgenii Lobzaev
A5030103632- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Fungal and yeast genetics research
- Chronic Disease Management Strategies
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Lysosomal Storage Disorders Research
- RNA Research and Splicing
- Enzyme Catalysis and Immobilization
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Machine Learning in Bioinformatics
- Biochemical and Molecular Research
- Sphingolipid Metabolism and Signaling
- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
- Glycosylation and Glycoproteins Research
University of Edinburgh
2021-2024
We describe construction of the synthetic yeast chromosome XI (synXI) and reveal effects redesign at non-coding DNA elements. The 660-kb genome project (Sc2.0) was assembled from synthesized fragments before CRISPR-based methods were used in a process bug discovery, redesign, repair, including precise compaction 200 kb repeat sequence. Repaired defects related to poor centromere function mitochondrial health associated with modifications regions. As part Sc2.0 design, loxPsym sequences for...
Whether synthetic genomes can power life has attracted broad interest in the biology field. Here, we report de novo synthesis of largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp yeast resulting from extensive genome streamlining and modification. We developed megachunk assembly combined with hierarchical integration strategy, which significantly increased accuracy flexibility construction. Besides drastic sequence changes, further manipulated 3D structure synIV to explore...
Type 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction intervention. While standard risk factors have shown good predictive performance, we show the use of blood-based DNA methylation information leads to significant improvement in 10-year T2D incidence risk. Previous studies been largely constrained by linear assumptions, cytosine–guanine pairs one-at-a-time binary outcomes. We present flexible approach (via an R...
Pioneering advances in genome engineering, and specifically writing, have revolutionized the field of synthetic biology, propelling us toward creation genomes. The Sc2.0 project aims to build first fully eukaryotic organism by assembling Saccharomyces cerevisiae. With completion chromosome VIII (synVIII) described here, this goal is within reach. In addition writing yeast genome, we sought manipulate an essential functional element: point centromere. By relocating native centromere sequence...
We describe the complete synthesis, assembly, debugging, and characterization of a synthetic 404,963 bp chromosome,
Abstract Engineering proteins is a challenging task requiring the exploration of vast design space. Traditionally, this achieved using Directed Evolution (DE), which laborious process. Generative deep learning, instead, can learn biological features functional from sequence and structural datasets return novel variants. However, most models do not generate thermodynamically stable proteins, thus leading to many non-functional Here we propose model called PRotein by Variational frEe eNergy...
Summary We describe construction of the 660 kilobase synthetic yeast chromosome XI ( synXI ) and reveal how redesign non-coding DNA elements impact cell. To aid from synthesized 5 to 10 fragments, we implemented CRISPR-based methods for crossovers in vivo used these an extensive process bug discovery, repair, including precise removal 200 kilobases unexpected repeated sequence. In , underlying causes several fitness defects were identified as modifications DNA, related centromere function...
Abstract Type 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction intervention. While standard risk factors have shown good predictive performance, we show the use of blood-based DNA methylation information leads to significant improvement in 10-year T2D incidence risk. Previous studies been largely constrained by linear assumptions, CpGs one-at-a-time, binary outcomes. We present flexible approach (via an R package,...
Summary Whether synthetic genomes can power life has attracted broad interest in the biology field, especially when are extensively modified with thousands of designer features. Here we report de novo synthesis largest eukaryotic chromosome thus far, synIV , a 1,454,621-bp Saccharomyces cerevisiae resulting from extensive genome streamlining and modification. During construction developed megachunk assembly combined hierarchical integration strategy, which significantly increased accuracy...
Engineering proteins with desired functions and biochemical properties is pivotal for biotechnology drug discovery. While computational methods based on evolutionary information are reducing the experimental burden by designing targeted libraries of functional variants, they still have a low success rate when protein has few or very remote homologous sequences. Here we propose an autoregressive model, called Temporal Dirichlet Variational Autoencoder (TDVAE), which exploits mathematical...
Abstract Enzymatic deficiencies cause the accumulation of toxic levels substrates in a cell and are associated with life-threatening pathologies. Restoring physiological enzymes by injecting recombinant version defective enzyme could provide viable therapeutic option. However, these replacement therapies have had limited success, as less catalytically active, immune response difficult to manufacture. Moreover, vast sequence design space makes finding desired properties extremely challenging....