Team abstracts can be found below, more information on the research and results can be found by going to the team homepage
(click team year or icon).
Cells in a local population have a wide range of responses to a given stimulus. This noisiness may be due to differences in extracelluar environment or intracellular molecular makeup. Yet these cells often need to coordinate and respond in a concerted way. Our project seeks to understand the complex intercellular interactions that must happen to produce such a specific community phenotype. Our goal is to create a synthetic framework that uses cellular communities to model collective behaviors emergent from individual autonomous rules.
Best Presentation (undergrad)
(Feb. 26, 2015) Feature on our innovative 2014 team in the UCSF News!
(Dec. 8, 2014) Read about the team in a featured interview on GetSynBio.
UCSF iGEM 2013 - Operation CRISPR: Deploying Precision Guided Tools to Target Unique Species in a Complex Microbiome
In microbial communities, bacterial populations are commonly controlled using indiscriminate, broad range antibiotics. There are few ways to target specific strains effectively without disrupting the entire microbiome and local environment. The goal of our project is to take advantage of a natural horizontal gene transfer mechanism in bacteria to precisely affect gene expression in selected strains. We combine bacterial conjugation with CRISPRi, an RNAi-like repression system developed from bacteria, to regulate gene expression in targeted strains within a complex microbial community. One possible application is to selectively repress pathogenic genes in a microbiome, leaving the community makeup unaffected. In addition, we use CRISPRi to lay the groundwork for transferring large circuits that enable complex functionality and decision-making in cells.
Advanced to World Championship
(Dec. 10, 2014) The 2013 project-turned ACS Syn Bio paper was featured in Chemical and Engineering News!
(Nov. 19, 2014) The 2013 team published their work -- Specific Gene Repression by CRISPRi System Transferred through Bacterial Conjugation -- in ACS Syn Bio, now available open source.
The 2012 UCSF iGEM team is investigating bacterial symbiosis. We hope to further the understanding of how two bacteria communicate in a mutualistic relationship. We have constructed experiments to demonstrate two methods of symbiosis. We were inspired by a paper that demonstrated tunable symbiosis of two auxotrophic strains of E. coli and attempted to regulate the population ratios of these strains (Kerner et al. 2012 PLoS ON. We have decided to build on this work to create strains of bacteria that can work together - lessening the metabolic burden on each one - to create some product. Our proof of priniciple products are easily identifiable (colorimetric) products such as the pigment violacein.
Many microbial cells form biofilms as a means of survival. Biofilms are formed when a large number of microbial cells aggregate together. This year, the UCSF iGEM team has engineered artificial biofilms via yeast cell surface display. We synthetically engineered S. cerevisiae to form tunable biofilm-like structures by inducing the display of adhesive proteins on their surface. By combining the natural yeast mating receptors – Aga1 and Aga2 – with adhesive proteins from a variety of organisms, we created several adhesive interactions among yeast cells. Our synthetic cell adhesions can serve as a model for biofilm formation and primitive multicellular structures.
The UCSF 2010 iGEM team aims to combat one of the leading causes of death worldwide - cancer. Globally, cancer accounts for nearly 1 of every 8 deaths. The number is projected to rise continuously as 1,530,000 new cancer cases are expected to be diagnosed just this year alone. We attempt to fight cancer by enhancing the immune system’s functions using synthetic biology. Specifically, our goal is to turn natural immune cells into Synthetic Killers that can:
- Detect cancer cells with Greater Precision
- Initiate killing responsively through Enhanced Signaling
- Destroy cancer cells effectively with Better Arsenal
Through our research, we hope to improve cancer therapies that involve the use of immune cells. Successfully engineered Synthetic Killers could be particularly useful for detecting tumors in early stages, which could bring new definition to the current use of immunotherapy. Introducing these Synthetic Killers in the early stages of cancer can prevent the disease from getting worse or even spreading elsewhere in the body.
Some eukaryotic cells, such as white blood cells, have the amazing ability to sense specific external chemical signals and move toward those signals. This behavior, known as chemotaxis, is a fundamental biological process crucial to such diverse functions as development, wound healing and immune response. In our project, we used a synthetic biology approach to manipulate signaling pathways that mediate chemotaxis in two model organisms: HL-60 (neutrophil-like) cells and the slime mold, Dictyostelium discoideum.
In doing so, we have demonstrated that we can regulate both the navigation and speed of our cells, as well as harness their ability to carry a payload.
Through our manipulations, we hope to better understand how these systems work, and eventually to build or reprogram cells that can perform useful tasks. Imagine, for example, therapeutic nanorobots that could home to a directed site in the body and execute complex, user-defined functions (e.g., kill tumors, deliver drugs, guide stem cell migration and differentiation). Alternatively, imagine bioremediation nanorobots that could find and retrieve toxic substances. Such cellular robots could be revolutionary biotechnological tools.
This year, our team attempted to engineer epigenetic control of gene expression. In eukaryotic cells, DNA is wound around nucleosomes, protein "spools" that consist of an octamer of histones. The DNA and protein together, termed chromatin, can be tightly packgaged (heterochromatin) or more loosely arranged (eucharomatin). The density of nucleosomal packaging is signaled by a host of histone modifying enzymes, and enforced by chromatin remodeling complexes. Euchromatin is accessible to the transcriptional machinery (active) while heterochromatin is inaccessible, and refractory to transcription (silenced).
In nature, the modulation of gene expression via the alteration of DNA structure is an incredibly powerful form of cellular memory. Indeed, epigenetic changes regulating genome-wide expression patterns can persist through multiple rounds of cell division and remain for the lifetime of the cell. This mechanism allows embryonic stem cells to differentiate into myriad cell types in higher eukaryotes.
For our project, we are establishing, characterizing and standardizing methods to engineer epigenetic control in the eukaryotic yeast Saccharomyces cerevisiae. To do so, we are taking endogenous proteins known to modify chromatin structure, such as Sir2, an NAD+ dependent histone deacetylase, and devising methods to control and direct their activity.
Best New Application Area
Best Poster (runner up)
UCSF iGEM 2007 - Location, Location, Location:
Directing Biology through Synthetic Assemblies and Organelles
Project 1: Protein Scaffolds as a Molecular Breadboard
Using synthetic protein scaffolds to control information flow of a kinase pathway in eukaryotic cells.
Project 2: Creating a Synthetic Organelle
Engineering phosphoinositide "barcodes" to create an intracellular membrane-bound chassis for
synthetic biology applications in eukaryotic cells.