ترغب بنشر مسار تعليمي؟ اضغط هنا

Top-down proteomics on a microfluidic platform

58   0   0.0 ( 0 )
 نشر من قبل Tuomas Knowles
 تاريخ النشر 2019
  مجال البحث فيزياء علم الأحياء
والبحث باللغة English




اسأل ChatGPT حول البحث

Protein identification and profiling is critical for the advancement of cell and molecular biology as well as medical diagnostics. Although mass spectrometry and protein microarrays are commonly used for protein identification, both methods require extensive experimental steps and long data analysis times. Here we present a microfluidic top down proteomics platform giving multidimensional read outs of the essential amino acids of proteins. We obtain hydrodynamic radius and fluorescence signals relating to the content of tryptophans, tyrosines and lysines of proteins using a combination of diffusional sizing of proteins, label-free detection and on-chip labelling of proteins with a latent fluorophore in the solution phase. We thereby achieve identification of proteins on a single microfluidic chip by separating and mapping proteins in multidimensional space based on their characteristic physical parameters. Our results have significant implications in the development of easy and rapid platforms to use for native protein identification in clinical and laboratory settings.



قيم البحث

اقرأ أيضاً

We propose a stochastic model for gene transcription coupled to DNA supercoiling, where we incorporate the experimental observation that polymerases create supercoiling as they unwind the DNA helix, and that these enzymes bind more favourably to regi ons where the genome is unwound. Within this model, we show that when the transcriptionally induced flux of supercoiling increases, there is a sharp crossover from a regime where torsional stresses relax quickly and gene transcription is random, to one where gene expression is highly correlated and tightly regulated by supercoiling. In the latter regime, the model displays transcriptional bursts, waves of supercoiling, and up-regulation of divergent or bidirectional genes. It also predicts that topological enzymes which relax twist and writhe should provide a pathway to down-regulate transcription. This article has been published in Physical Review Letters, May 2016.
118 - Ziqing Wang , Ming Li 2011
Membrane tubes are important elements for living cells to organize many functions. Experiments have found that membrane tube can be extracted from giant lipid vesicles by a group of kinesin. How these motors cooperate in extracting the fluid-like mem brane tube is still unclear. In this paper, we propose a new cooperation mechanism called two-track-dumbbell model, in which kinesin is regarded as a dumbbell with an end (tail domain) tightly bound onto the fluid-like membrane and the other end (head domain) stepping on or unbinding from the microtubule. Taking account of the elasticity of kinesin molecule and the exclude volume effect of both the head domain and the tail domain of kinesin, which are not considered in previous models, we simulate the growth process of the membrane tube pulled by kinesin motors. Our results indicate that motors along a single microtubule protofilament can generate enough force to extract membrane tubes from vesicles, and the average number of motors pulling the tube is about 8~9. These results are quite different from previous studies (Ref. cite{camp.08}), and further experimental tests are necessary to elucidate the cooperation mechanism.
We discuss a polymer model for the 3D organization of human chromosomes. A chromosome is represented by a string of beads, with each bead being colored according to 1D bioinformatic data (e.g., chromatin state, histone modification, GC content). Indi vidual spheres (representing bi- and multi-valent transcription factors) can bind reversibly and selectively to beads with the appropriate color. During molecular dynamics simulations, the factors bind, and the string spontaneously folds into loops, rosettes, and topologically-associating domains (TADs). This organization occurs in the absence of any specified interactions between distant DNA segments, or between transcription factors. A comparison with Hi-C data shows that simulations predict the location of most boundaries between TADs correctly. The model is fitting-free in the sense that it does not use Hi-C data as an input; consequently, one of its strengths is that it can -- in principle -- be used to predict the 3D organization of any region of interest, or whole chromosome, in a given organism, or cell line, in the absence of existing Hi-C data. We discuss how this simple model might be refined to include more transcription factors and binding sites, and to correctly predict contacts between convergent CTCF binding sites.
Top-down causation has been suggested to occur at all scales of biological organization as a mechanism for explaining the hierarchy of structure and causation in living systems. Here we propose that a transition from bottom-up to top-down causation - - mediated by a reversal in the flow of information from lower to higher levels of organization, to that from higher to lower levels of organization -- is a driving force for most major evolutionary transitions. We suggest that many major evolutionary transitions might therefore be marked by a transition in causal structure. We use logistic growth as a toy model for demonstrating how such a transition can drive the emergence of collective behavior in replicative systems. We then outline how this scenario may have played out in those major evolutionary transitions in which new, higher levels of organization emerged, and propose possible methods via which our hypothesis might be tested.
Considering a multi-pathway structure in a light-harvesting complex of photosynthesis, we investigate the role of energy-level mismatches between antenna molecules in transferring the absorbed energy to a reaction center. We find a condition in which the antenna molecules faithfully play their roles: Their effective absorption ratios are larger than those of the receiver molecule directly coupled to the reaction center. In the absence of energy-level mismatches and dephasing noise, there arises quantum destructive interference between multiple paths that restricts the energy transfer. On the other hand, the destructive interference diminishes as asymmetrically biasing the energy-level mismatches and/or introducing quantum noise of dephasing for the antenna molecules, so that the transfer efficiency is greatly enhanced to near unity. Remarkably, the near-unity efficiency can be achieved at a wide range of asymmetric energy-level mismatches. Temporal characteristics are also optimized at the energy-level mismatches where the transfer efficiency is near unity. We discuss these effects, in particular, for the Fenna-Matthews-Olson complex.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا