Tag Archives: biocontrol systems

Genome Integrity and the Unsafe Genes

DARPA created the Safe Genes program to gain a fundamental understanding of how gene editing technologies function; devise means to safely, responsibly, and predictably harness them for beneficial ends; and address potential health and security concerns related to their accidental or intentional misuse. Today, DARPA announced awards to seven teams that will pursue that mission, led by: The Broad Institute of MIT and Harvard; Harvard Medical School; Massachusetts General Hospital; Massachusetts Institute of Technology; North Carolina State University; University of California, Berkeley; and University of California, Riverside. DARPA plans to invest $65 million in Safe Genes over the next four years as these teams work to collect empirical data and develop a suite of versatile tools that can be applied independently or in combination to support bio-innovation and combat bio-threats.

Gene editing technologies …[can] selectively disable cancerous cells in the body, control populations of disease-spreading mosquitos, and defend native flora and fauna against invasive species, among other uses. The potential national security applications and implications of these technologies are equally profound, including protection of troops against infectious disease, mitigation of threats posed by irresponsible or nefarious use of biological technologies, and enhanced development of new resources derived from synthetic biology, such as novel chemicals, materials, and coatings with useful, unique properties.

Achieving such ambitious goals, however, will require more complete knowledge about how gene editors, and derivative technologies including gene drives, function at various physical and temporal scales under different environmental conditions, across multiple generations of an organism. In parallel, demonstrating the ability to precisely control gene edits, turning them on and off under certain conditions or even reversing their effects entirely, will be paramount to translation of these tools to practical applications…

Each of the seven teams will pursue one or more of three technical objectives: develop genetic constructs—biomolecular “instructions”—that provide spatial, temporal, and reversible control of genome editors in living systems; devise new drug-based countermeasures that provide prophylactic and treatment options to limit genome editing in organisms and protect genome integrity in populations of organisms; and create a capability to eliminate unwanted engineered genes from systems and restore them to genetic baseline states. Safe Genes research will not involve any releases of organisms into the environment; however, the research—performed in contained facilities—could inform potential future applications, including safe, predictable, and reversible gene drives….

A Harvard Medical School team led by Dr. George Church seeks to develop systems to safeguard genomes by detecting, preventing, and ultimately reversing mutations that may arise from exposure to radiation. This work will involve creation of novel computational and molecular tools to enable the development of precise editors that can distinguish between highly similar genetic sequences. The team also plans to screen the effectiveness of natural and synthetic drugs to inhibit gene editing activity.

A North Carolina State University (NCSU) team led by Dr. John Godwin aims to develop and test a mammalian gene drive system in rodents. The team’s genetic technique targets population-specific genetic variants found only in particular invasive communities of animals. If successful, the work will expand the tools available to manage invasive species that threaten biodiversity and human food security, and that serve as potential reservoirs of infectious diseases affecting native animal and human populations….

A University of California, Berkeley team led by Dr. Jennifer Doudna will investigate the development of novel, safe gene editing tools for use as antiviral agents in animal models, targeting the Zika and Ebola viruses. The team will also aim to identify anti-CRISPR proteins capable of inhibiting unwanted genome-editing activity, while developing novel strategies for delivery of genome editors and inhibitors….

A University of California, Riverside team led by Dr. Omar Akbari seeks to develop robust and reversible gene drive systems for control of Aedes aegypti mosquito populations.

Excerpts from Building the Safe Genes Toolkit, DARPA Press Release, July 19, 2017

Robo-Cells Killing Bacteria

Fuligo septica, the "dog vomit" slime mold. image from wkipedia

Johns Hopkins University researchers are setting out to design and test self-directed microscopic warriors that can locate and neutralize dangerous strains of bacteria…[The goal] s to devise a prototype biocontrol system that can dispatch single-cell fighters to track down and engulf specific pathogens, rendering them harmless. The funding was awarded by the Defense Advanced Research Projects Agency, commonly called DARPA.

Possible first targets in this proof-of-concept project include Legionella, the bacteria that cause Legionnaire’s disease; and Pseudomonas aeruginosa, a bacterial strain that is the second-leading cause of infections found in hospitals. If the project succeeds, these tiny infection-fighters might one day be dispatched to curtail lethal microbes lurking in medical settings. Eventually, they could also be used to cleanse contaminated soil or possibly defend against bioterror attacks.

An important goal of the project is that each of the proposed soldier cells must carry out its own mission without relying on step-by-step commands from a remote human operator.

“Once you set up this biocontrol system inside a cell, it has to do its job autonomously, sort of like a self-driving car,” said Pablo A. Iglesias.”…In a similar way, the biocontrol systems we’re developing must be able to sense where the pathogens are, move their cells toward the bacterial targets, and then engulf them to prevent infections among people who might otherwise be exposed to the harmful microbes.”

These experts plan to biologically embed search-and-surround orders within a familiar type of amoeba cell called Dictyostelium discoideum [slime mold]. These widely studied microbes, commonly found in damp soil such as riverbeds, typically engulf and dine on bacteria, which are much smaller.  “These amoebas possess receptors that can detect the biochemical ‘scents’ emitted by bacteria,” Robinson said. “Our goal is to use concepts from control theory to design a ‘super amoeba’ that can recognize a particular bad guy—a specific type of disease-causing bacteria—and then move toward and attack these target cells.”  Robinson added: “The plan is to develop amoebas that are super-sensitive to these bacterial signals and home in on them as though they were a plate piled high with fresh chocolate chip cookies. The goal is to make these amoebas behave as though this is the most natural thing to do.”.. But if the project is successful, the researchers say the single-cell fighters could eventually be introduced into the cooling and ventilation system in a hospital, where they could feast on the bacteria that are currently causing dangerous infections. One possible method of introducing the infection fighters into such systems might be through use of a spray solution.

Iglesias noted that initial efforts will focus on bacteria lurking outside, not within the body.  “In this contract, we are not targeting bacteria in human blood,” he said, “but the hope is that the techniques we develop would ultimately be useful for that.”

Excerpts from Phil Sneiderman, Johns Hopkins researchers aim to design self-driving cells to pursue deadly bacteria, John Hopkins University, Feb. 2, 2016