SynBioFromLeukipposInstitute

by

Nicole Rusk

"Simple two- and three-component circuits induce polarization in yeast cells.

Unlike human engineers, nature does not work from the top down. We build structures mostly according to a blueprint of the final product; but biology takes a bottom-up approach and uses local molecular interactions to construct global structures and order. Wendell Lim from the University of California in San Francisco and Chao Tang from Peking University wanted to get at the underlying rules that biological systems play by.

“We wanted to look at biological regulation from an inverse approach,” explains Lim, “not asking how one particular system performs a function of interest, but what are all the possible ways a function of interest can be accomplished.” He adds that in the post-genomic era, scientists have identified the molecular parts for many systems, but how the parts work together to accomplish a given function is much less well understood.

In particular, Lim and Tang focused on cell polarization, which Tang, a physicist, describes as “symmetry breaking via self-organization.” Their goal was to find the simplest network that accomplishes the task. Spatial organization in a cell is the key for many downstream behaviors such as motility.
...."
http://bit.ly/UufZzI

Comment to:

*Designing Synthetic Regulatory Networks Capable of Self-Organizing Cell Polarization*

by
Angela H. Chau Jessica M. Walter, Jaline Gerardin, Chao Tang, and Wendell A. Lim

"How cells form global, self-organized structures using genetically encoded molecular rules remains elusive. Here, we take a synthetic biology approach to investigate the design principles governing cell polarization. First, using a coarse-grained computa- tional model, we searched for all possible simple networks that can achieve polarization. All solutions contained one of three minimal motifs: positive feed- back, mutual inhibition, or inhibitor with positive feedback. These minimal motifs alone could achieve polarization under limited conditions; circuits that combined two or more of these motifs were signifi- cantly more robust. With these design principles as a blueprint, we experimentally constructed artificial polarization networks in yeast, using a toolkit of chimeric signaling proteins that spatially direct the synthesis and degradation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Circuits with combinato- rial motifs yielded clear foci of synthetic PIP3 that can persist for nearly an hour. Thus, by harnessing localization-regulated signaling molecules, we can engineer simple molecular circuits that reliably execute spatial self-organized programs."
http://bit.ly/Uc58vo

The technique combines computer-aided design software with nanoscale fabrication technology.

*I just learned about a very interesting iGEM project for 2013*!

It is a follow up of an outstanding cell paper (see below) about a computational model for a cell.. This paper applies oriented programming. I think languages like objective-c (Apple - Xcode) are very good suited to modulate biological phenomena, as they reflect the biological duality of form and function.

http://bit.ly/YT9nDX

Ref. original paper in Cell:
*A Whole-Cell Computational Model Predicts Phenotype from Genotype*

by
Jonathan R. Karr, Jayodita C. Sanghvi, Derek N. Macklin, Miriam V. Gutschow, Jared M. Jacobs, Benjamin Bolival, Nacyra Assad-Garcia, John I. Glass, Markus W. Covert

"Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology that computational approaches are poised to tackle. We report a whole-cell computational model of the life cycle of the human pathogen Mycoplasma genitalium that includes all of its molecular components and their interactions. An integrative approach to modeling that combines diverse mathematics enabled the simultaneous inclusion of fundamentally different cellular processes and experimental measurements. Our whole-cell model accounts for all annotated gene functions and was validated against a broad range of data. The model provides insights into many previously unobserved cellular behaviors, including in vivo rates of protein-DNA association and an inverse relationship between the durations of DNA replication initiation and replication. In addition, experimental analysis directed by model predictions identified previously undetected kinetic parameters and biological functions. We conclude that comprehensive whole-cell models can be used to facilitate biological discovery."

see also this awesome hangout:
Dawn of Virtual Cell Biology: A Whole-Cell Computational Model Predicts Phenotype from Genotype

"A journal club and author interview about the recent paper "A Whole-Cell Computational Model Predicts Phenotype from Genotype", Karr et al., 2012, about a whole cell simulation. Stephen Larson presents a 45 minute overview of the paper and authors Jonathan Karr and Jayodita Sanghvi answer questions and clarify the paper. Organized by the members of OpenWorm.org"
http://bit.ly/MpWUx8

http://bit.ly/VIYa6R

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Carlos G. Acevedo-Rocha, Gang Fang3, Markus Schmidt, David W. Ussery, Antoine Danchin

"A central undertaking in synthetic biology (SB) is the quest for the ‘minimal genome’. However, ‘minimal sets’ of essential genes are strongly context-dependent and, in all prokaryotic genomes sequenced to date, not a single protein-coding gene is entirely conserved. Furthermore, a lack of consensus in the field as to what attributes make a gene truly essential adds another aspect of variation. Thus, a universal minimal genome remains elusive. Here, as an alternative to defining a minimal genome, we propose that the concept of gene persistence can be used to classify genes needed for robust long-term survival. Persistent genes, although not ubiquitous, are conserved in a majority of genomes, tend to be expressed at high levels, and are frequently located on the leading DNA strand. These criteria impose constraints on genome organization, and these are important considerations for engineering cells and for creating cellular life-like forms in SB."

http://bit.ly/VXOqCn

Craig Venter, CEO & President, Synthetic Genomics, shares the latest advancements in synthetic genomic research and technology. According to Venter, synthetic biological organisms are not far away.

- 47min video with Craig Venter http://bit.ly/127aY6Q

Video: Three-Dimensional Structures Self-Assembled from DNA Bricks http://bit.ly/VOdwn8

see also these 2 new communities on G+
Synthetic Biology
https://plus.google.com/communities/110080235428400987829?hl=en
Biological Computing
https://plus.google.com/communities/117578997424311496437?hl=en

via +Carlos Toscano Ochoa 1 year old, but still interesting work by an iGEM team:

Team Sevilla

"Although our project is pretty ambitious, it is also certainly feasible. We are going to build circuits based on collections of different bacteria strains, where each strain works as a logic gate. A logic gate is the basic component of an electronic circuit, such as AND, OR or XOR, and it exchanges information with the others.Combining the correct strains and using certain chemical substances as system inputs we can manipulate a bacterial community into performing complex functions.
To achieve our goal we are going to define a standard of programming modularized biological circuits, where a community of bacteria from different but interconnected strains form a physically independent module. Combining different modules in this way makes it possible to recycle strains and substances. To implement this system, the key is to standardise the inter-modular communication substances. This is exactly what we are going to do: we are going to define a substance, which we have named the Universal BioBit (or Ubbit for short), that will be the element of communication between modules. Just like that, any research group could use the modules created by any other group and combine them with their own without the necessity of knowing how it internally works, just by using the Ubbit standard."

http://bit.ly/12fMYPa

"Johns Hopkins researchers have used a small synthetic molecule to stimulate cells to move and change shape, bypassing the cells' usual way of sensing and responding to their environment.

The experiment pioneers a new tool for studying cell movement, a phenomenon involved in everything from development to immunity to the spread of cancer.

"We were able to use synthetic molecules small enough to slip inside the cell and activate a chemical reaction controlling cell movement, bypassing most of the steps that usually lead up to this reaction," says Dr. Andre Levchenko, a professor at the Johns Hopkins University School of Medicine's Institute for Cell Engineering, whose lab collaborated with that of Takanari Inoue, also from the school of medicine, on the study.

"As a result, we came up with a new model to describe one of the more fundamental and important cellular processes and a better understanding of cell movements critical for cancer progression and immune response." A report on the study was published Nov. 26 on the website of the Proceedings of the National Academy of Sciences.
.."

http://bit.ly/RHh24Y

In the first of an occasional series of Cell Annotated Classics, Konrad Hochedlinger makes notes in the margins of the original iPS paper from Nobel Prize winner Shinya Yamanaka, published in Cell in 2006. Konrad comments on his first impressions of the paper and how the field has moved on since then as a result of this groundbreaking study.
http://download.cell.com/images/edimages/Cell/annot_class_dec07.pdf

Video http://bit.ly/TMoSpR

CORNELL (US) — A new material made from synthetic DNA is so soft that it can flow like a liquid and then, strangely, return to its original shape.