Biology subjects

Yusuf, A.

Publications and source records attributed to Yusuf, A..

5 recordsLinked to original sources

bioRxiv2024

Results of the Protein Engineering Tournament: An Open Science Benchmark for Protein Modeling and Design

The grand challenge of protein engineering is the development of computational models to characterize and generate protein sequences for arbitrary functions. Progress is limited by lack of 1) benchmarking opportunities, 2) large protein function datasets, and 3) access to experimental protein characterization. We introduce the Protein Engineering Tournament--a fully-remote competition designed to foster the development and evaluation of computational approaches in protein engineering. The tournament consists of an in silico round, predicting biophysical properties from protein sequences, followed by an in vitro round where novel protein sequences are designed, expressed and characterized using automated methods. Upon completion, all datasets, experimental protocols, and methods are made publicly available. We detail the structure and outcomes of a pilot Tournament involving seven protein design teams, powered by six multi-objective datasets, with experimental characterization by our partner, International Flavors and Fragrances. Forthcoming Protein Engineering Tournaments aim to mobilize the scientific community towards transparent evaluation of progress in the field. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/606135v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@8f9769org.highwire.dtl.DTLVardef@11da734org.highwire.dtl.DTLVardef@1cc51c0org.highwire.dtl.DTLVardef@10b3c27_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Prophages block cell surface receptors to ensure survival of their viral progeny

In microbial communities, viruses compete for host cells to infect, and thus evolved diverse ways to inhibit their competitors. One mechanism is Superinfection exclusion (Sie), whereby a virus that has established an infection prevents a secondary infection. We identified a Pseudomonas prophage Sie protein that alters pilus dynamics through the pilus assembly chaperone, PilZ. This protein, known as Zip for PilZ interacting protein, does not abrogate pilus activity, but fine tunes it, providing strong phage resistance without a fitness cost. This tuning is modulated through quorum sensing, which coordinates Zip production in concert with bacterial cell density to ensure maximal protection when bacterial populations are at the highest risk of phage infection. Most notably, Zip activity prevents internalization and destruction of phage progeny. We refer to this as the "anti-Kronos effect" after the Greek god who devoured his own children and show that it is a conserved feature of diverse prophage-encoded Sie systems.

microbiology↗

bioRxiv2023

Teaching transposon classification as a means to crowd source the curation of repeat annotation - a tardigrade perspective

The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences. However, manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd sourcing efforts could offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries. Here, we present an example of such crowd sourcing effort developed through both in-person and online courses built around a collaborative peer-reviewed teaching process that can be used as teaching reference guide for similar projects. The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs: A hidden treasure awaits discovery within non-model organisms.

evolutionary biology↗

bioRxiv2019

Nutritional Status and its Related Factors in Khalwa Residents, Khartoum state, Sudan.

IntroductionKhalwa is an Islamic educational institution, known as such in Sudan and called elsewhere Koranic institution. Our research aimed to assess the nutritional status and its related factors among Khalwa residents in Khartoum State.\n\nMethodsA facility-based cross-sectional study was implemented in two localities of Khartoum State. A multistage sampling technique was used to selected 1273 residents. At first level, four khalwa were selected in the seven localities of Khartoum State through a stratified random sampling technique. At second level, in each of the khalwa selected, all the residents fulfilling the inclusion and exclusion criteria were included in the study. The collected data were firstly summarized numerically and graphically. Then, associations/differences among variables were determined through chi-square tests and ANOVA. A multinomial logistic regression established the relationship between the nutritional status of the residents and its related factors. All statistical tests were considered statistically significant when p< 0.05.\n\nResultsThe age of 1273 residents varied from 6 to 60 years with an average age of 15 years. Their mean body mass index (BMI) of 16.6{+/-}3.4 ranged from 7.8 to 34.0. 73.8% (939/1272) of the residents were undernourished, 23.9% (23.9%, 309/1272) were well nourished and 2.3% (29/1272) were overweight/obese. The statistically significant factors related to the nutritional status of the residents were age (under-nourished p=0.000; well-nourished p=0.004), status in the khalwa (p=0.001 vs p=0.075), resting time (p=0.002 vs p=0.038), practices of hand washing (p=0.165 vs p=0.011) and exercising (p=0.032 vs p=0.027). The food practices, despite their contributions to the model, were not statistically significant (p > 0.05).\n\nDiscussionThe nutritional status of khalwa should be translated urgently in a community-directed intervention based on a partnership involving the affected communities, political and administrative authorities, national, bilateral and international donors to overcome the burden of malnutrition.

epidemiology↗

bioRxiv2017

Structural Basis of Mitochondrial Receptor Binding and GTP Driven Conformational Constriction by Dynamin-Related Protein 1

Mitochondrial inheritance, genome maintenance, and metabolic adaptation all depend on organelle fission by Dynamin-Related Protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogs Mitochondrial Dynamics 49 and 51 (MID49/MID51) and Mitochondrial Fission Factor (MFF), but the mechanisms by which these proteins recruit DRP1 and regulate its activities are unknown. Here we present a cryoEM structure of human, full-length DRP1 bound to MID49 and an analysis of structure- and disease-based mutations. We report that GTP binding allosterically induces a remarkable elongation and rotation of the G-domain, Bundle-Signaling Element (BSE) and connecting hinge loops of DRP1. In this nucleotide-bound conformation, a distributed network of multivalent interactions promotes DRP1 copolymerization into a linear filament with MID49, MID51 or both. Subsequent GTP hydrolysis and exchange within the filament leads to receptor dissociation, shortening through disassembly, and concomitant curling of DRP1 oligomers into closed rings. The dimensions of the closed DRP1 rings are consistent with DRP1-constricted mitochondrial tubules observed in human cells. These structures are the first views of full-length, receptor- and nucleotide-bound dynamin-family GTPases and--in comparison with nucleotide-free crystal structures--teach us how these molecular machines perform mechanical work through nucleotide-driven allostery.

biophysics↗