The complexity of biological system urgently demands computational models which can produce new understanding and new medicine. Keeping in view Khwarizmi Science society and Journal Club at IRCBM, COMSATS jointly presents a seminar on agent based modeling approach in Investigating Multiscale Tumorigenesis in the Warburg Effect.
Early stage tumorigenesis includes the formation of glycolytic cells in the tissue. However, the precise multi-scale processes underlying this transformation of healthy epithelial cells into tumorigenic glycolytic phenotypes, continues to be a matter of debate. In this work, we investigate this cellular transformation by using an agent based modeling approach and decode a multifactorial mechanism which upon triggering may lead to the onset of tumorigenesis
This series of two classroom lectures will cover the fundamentals of lasers: how they work, what are their characteristics and what are their important types. We will also discuss some of their exciting and useful applications in industry, medicine, communications, optical disks and art and culture. This is in celebration of 50 years of this exciting discovery. Science students (B.Sc. level) are especially welcome to attend. The lectures are in fact part of a semester long course on Atomic and Laser Physics.
How cell fates are established and how identities of different cell types are maintained during development of multi-cellular eukaryotes are questions of extreme biological significance at the heart of development. A single-celled zygote undergoes many rounds of mitotic divisions which ultimately lead to generation of over 200 different specialized cell types in human body during development. Although, each cell type contains same basic genetic information (DNA), yet their identity is different from one another which are maintained throughout development. It is known that differential gene expression programs lead to different cell lineages and each cell type remembers its identity due to maintenance of cell type specific gene expression program referred to as transcriptional cellular memory. Transcriptional memory involves changes in the chromatin state of lineage specific genes; changes that can persist through DNA replication and mitosis, which means they are inherited from mother to daughter cells. Such heritable changes are called epigenetic modifications and can be covalent marks on DNA and/or histones, and therefore would not alter the basic genetic information in a cell. However, epigenetic changes may either activate or silence the expression of lineage specific genes and set the stage for differential gene expression among different cell type. This explains how cells with same DNA can acquire different identity which is maintained through epigenetic inheritance during development. In Drosophila melanogaster (fruit flies), genetic analyses have uncovered two groups of genes, the Polycomb Group (PcG) and the trithorax Group (trxG), responsible for maintaining gene expression patterns stably and heritably. Importantly, PcG and trxG proteins are evolutionary conserved and most of our knowledge about their function was pioneered from studies in Drosophila. Molecular analysis showed that many of the proteins encoded by the PcG and trxG act in large complexes, and modify the local properties of chromatin to maintain transcriptional repression (PcG) or activation (TrxG) of their target genes. My lecture will primarily focus on introducing epigenetics, transcriptional cellular memory and how they affect our development.
Semiconductor nanowires (NWs) are attracting wide interest due to their unique physical properties and potential for application in nanodevices. NWs can be obtained by a number of growth methods, and their highly anisotropic growth originates by the presence of a metal particle, the catalyst, that determines the position and the diameter of the nanostructure. The most widely used catalyst is gold. The growth mechanism of catalyst assisted nanowires involves the incorporation of material both impinging on the catalyst particle and diffusing from the free substrate surface to the sidewalls of the wire. The interplay of these two phenomena is critical especially for the growth of alloy semiconductor compound NWs and one dimensional (1-D) heterostructure. Difference in the surface mobility between the constituents could give compositional inhomogeneities in alloy NWs and degradation of the interface sharpness in 1-D heterostructure. The systematic presence of a metal particle at the NWs tip could be exploited in single NW devices. Moreover, one of the most interesting characteristic of the III-V NWs grown by catalyst assisted self assembling is the peculiarity of having an hexagonal lattice structure (wurtzite), while their bulk and epitaxial parent materials have the cubic structure (zinc blend). In our laboratory we have synthesized GaAs NWs by molecular beam epitaxy (MBE) either using a thin gold, manganese, Ga layer as the growth catalyst or without any catalyst. In this talk some of the basics of NWs, their growth and potential applications will be covered.
Cells reside and operate in a complex and dynamic extra-cellular matrix. The mechanical, structural and chemical properties of the matrix regulate a variety of cellular functions including signaling, adhesion, migration as well as invasion and metastasis in tumor systems. Unfortunately cell-matrix interactions have traditionally been studied in the context of artificial 2D environments, which are far from in vivo conditions. As a result, our understanding of the complex interactions at the cell-matrix interface has been quite limited. In particular, the mechano-chemical effects of the matrix, the proteolytic pathways and surface receptor dynamics on a 3D surface that are critical in invasion and tumor metastasis, and can not be fully studied in a 2D environment. In order to overcome the limited powers of observation in 2D, we utilize a combination of high resolution and high throughput confocal microscopy, bulk and micro-rheological measurements and multi-scale simulations rooted in statistical and continuum mechanics. Using an interdisciplinary approach allows us to understand and quantify the mechanical and chemical roles of the matrix in regulating signaling, adhesion and motility. Our results demonstrate that both cell structure and cell function are strikingly different in 3D than in 2D and that cellular response to minor mechanical changes in its extra-cellular environment is amplified in 3D than in 2D environments. Our experimental results are complemented by multi-scale simulations, that probe the physical foundations of cell-matrix interactions from the nano to the macro level. Our hybrid approach, combining high-resolution experimental and computational techniques demonstrates how a balance of cellular parameters (e.g. integrin expression and MMP activity) co-operate with matrix properties (e.g. composition, stiffness and porosity) to regulate adhesion, invasion and motility of tumor cells in native like environments.
The controlled arrangement of DNA molecules on surfaces represents one challenging contribution of nanotechnology to biology and medicine. In particular, one of the open issues in the field of DNA-based sensors is detecting the hybridization process with high precision in a real-life biological environment. Towards this end, we have studied the hybridization of single stranded (ss)-DNA anchored on a gold surface using the increase in height of the molecules upon hybridization with a label free target which is due to the much larger rigidity of ds- vs. ss-DNA. Nano-scale ss-DNA patches are assembled within oligo-ethylene-glycol terminated alkylthiol self-assembled monolayer on a gold substrate using nanografting (an atomic force microscopy-based nanolithography technique). Differential height measurements indicate that ss-DNA nano-patches do not show significant increase in height upon hybridization with complementary strands in high density regime. Moreover, the advantage of this system for biosensors and genomics applications will be discussed briefly in the end.
Quantum computers have occupied the imagination, time, energy and resources of many researchers worldwide. About ten years after the first prototypes became implementable in labs worldwide, are we still too far removed from a practical, useful realization? This talk will cover the basics of what quantum computers are, what they (or might) look like and why is there so much hype about them. This will be an elementary introduction aimed at the college-level science students.
General Relativity tells us that all massive objects deform the backgrounds into which they are placed so that the very shape of space is changed by their presence. If, in addition, these objects happen to be charged, they give rise to a flux which distorts the background still further. In the talk, we will apply these simple ideas to gather information about the elusive 11-dimensional M-theory which gives rise to string theory. We will try to categorize some of the geometries that are allowed in M-Theory by studying what happens to a background when stable hyper-dimensional objects called BPS M-branes are brought into it.