Synthetic Biology: Engineering Life

Synthetic Biology Basics

• At its core, synthetic biology involves engineering living cells to perform useful functions.
• Synthetic biologists alter an organism's DNA to make it behave according to specifications.
• An example application of synthetic biology includes creating cells that can treat diseases, sense toxic compounds, or make valuable drugs.
• The goal of synthetic biology is to write DNA that instructs a cell or organism to behave in a designed manner.
• Synthetic biologists design a DNA portion and combine it with an existing cell or organism to achieve desired behavior.

Timeline of Synthetic Biology

• The discovery that DNA is the hereditary material was made in 1944 by Avery.
• Sanger Sequencing was developed in 1975.
• Scientists are synthesizing DNA assemblies, inserting them into bacteria, and observing their reproduction, which demonstrates synthetic biology's rapid current progress.

Applications in Healthcare

• Synthetic biology can be applied to diagnose diseases by inserting gene circuits into the human body or patient-derived cells.
• Synthetic networks using viruses, bacteria, or mammalian cells can be added to patient-derived tissue or body fluids to detect disease states.
• Synthetic biology can screen for pharmaceutical compounds by inserting synthetic circuits into various organisms to mimic disease-related states.
• Synthetic gene networks can monitor the activation or inactivation of transmembrane receptors as potential drug targets.
• Synthetic biology can enhance the manufacturing of pharmaceuticals and other biologics.
• Synthetic biology can improve treatments like gene therapy, cell therapy, CAR T-cell immunotherapy, bacterial-based therapy for cancer, and bacteriophage-based therapy for infectious diseases.

Creating Synthetic Cells

• In 2010, the J. Craig Venter Institute designed, synthesized, and assembled a 1.08-Mbp Mycoplasma mycoides genome from digitized sequence information.
• The synthetic genome was transplanted into a Mycoplasma capricolum recipient cell to create new Mycoplasma mycoides cells controlled by the synthetic chromosome.
• The new cells have expected phenotypic properties and continuous self-replication capabilities.
• A synthetic M. mycoides genome was assembled from 1078 overlapping DNA cassettes in three steps in yeast.

Essential Elements of Synthetic Biology

• DNA synthesis involves chemical production of DNA strands without a pre-existing template.
• Standardization aims to generate reusable components, and helps streamline research and design
• Abstraction manages detailed information when building complex systems.

Abstraction Hierarchy

• The highest abstraction layer is the system, a cellular black box.
• The device creates a specific function like sensing a chemical or creating a scent.
• Parts make up the devices, and are ways to sense chemicals or control scent output.
• DNA sequences are the non-abstract parts needed.

Core concepts in Synthetic Biology

• Abstraction: Information from DNA to engineered multicellular systems.
• Decoupling and Abstraction: Modular design for reusing components and devices in multiple systems.
• C6 homoserine lactone signaling modules have negative feedback regulations.

Tools and Applications of Synthetic Biology

• Molecular biology tools like genetic activators, repressors, recombinases, genome editing, and synthetic transcription factors are used in synthetic biology.
• Genetic circuits assembled from parts enable dynamic gene expression, tight gene control, memory, and Boolean logic operations.
• Synthetic biology finds applications in diagnostics, discovery, and therapeutics.

Genome Refactoring

• Genome refactoring involves redesigning and rebuilding a genome to optimize it for specific purposes.
• The process involves eliminating nonessential genes, removing native regulation, and randomizing codons.

Predictability of Synthetic Biology

• Synthetic biology aims to advance plant biology similarly to the electronics revolution.
• What sets synthetic biology apart, is that it can produce predictable functions in genetic circuits using standardized componets.

Electronic plants

• Plants are similar to electrical circuits
• This includes interconnects, wires, and devices.

Cell Circuits

• Cell circuits are where cells signal one another to control cellular processes.
• Concentrations are the main difference

Genetic Circuits

• Genetic circuit engineering synthesizes unnatural DNA segments encoding proteins or RNA molecules that control each other's levels.
• Can program the functionality, performance, and behavior of other cells

Toggle Swith

• Genetic toggle switch comprised of two genes
• There is a positive repressors and activators