Challenges of Particular Interest to Me


As a scientist, I am driven by the power of technological breakthroughs to make positive change for humanity. While I also take immense pleasure in the artistic/creative aspects of technology design, my motivation is centered on helping people and on protecting the future of the human species. For this reason, I am interested in a wide array of contemporary challenges as described in this outline. Because I am a synthetic biologist and synthetic biology has many applications, I have the ability to explore solutions to such diverse challenges despite their highly multidisciplinary nature.

That said, one of the tools in any good researcher’s repertoire is collaboration. Since I am just one person, my knowledge can only go so deep in so many areas. Interdisciplinary projects are much more likely to succeed when experts from multiple areas work together. So, I leverage collaboration extensively when carrying out my projects and will continue to do so in the future.

It should be noted that, though I am publicly presenting a number of conceptual explanations of possible solutions to important problems via this list, I have deliberately stated them in somewhat vague language to prevent their public disclosure from precluding outside investment.

I am sharing this list as a way of increasing my likelihood of connecting with potential collaborators over time and as a method of inspiring others to consider how they too might contribute to building a bright future.

I chose the featured image of a Martian-hued rendering of the Anasazi Cliff Palace at Mesa Verde National Park as a symbolic tribute to the creative and culturally rich spirit of humanity, an homage to where we have come from, and a hopeful indication of where we might go in the future.

Infectious Disease Burden in Developing Countries

  • Especially malaria, tuberculosis, and HIV.
  • Translational strategies for dissemination are key.
  • Some possible solutions:
    • Gene drives to prevent mosquitos from carrying pathogens
    • Inexpensive home diagnostics
    • Rapid inexpensive biomanufacturing of treatments
    • Thermostable treatments and vaccines
    • Inexpensive immune enhancement gene therapies
    • Rapid inexpensive biomanufacturing of vaccines

Antibacterial Resistance

  • Especially highly concerning pathogens such as carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter, Clostridioides difficile, and drug-resistant Neisseria gonorrhoeae.
  • Adaptability and rapid generation of new solutions are key.
  • Some possible solutions:
    • Adaptable probiotic treatments
    • Rational design of phage therapies
    • Diversified phage therapy production platforms
    • Lysogenic phage therapies for widespread resistance shutdown and/or bactericide
    • Sentinel bacteria for detection and elimination of resistance in environment (esp. livestock and wastewater)
    • Bacterial conjugation for elimination of resistance in environment
    • Immune enhancement gene therapies
    • Rapid inexpensive biomanufacturing of vaccines
    • Rapid vaccine discovery platforms
    • Inexpensive home diagnostics

Affordable Gene Therapy Manufacturing

  • Many existing gene therapy delivery vehicles are extremely expensive to produce, so treatments are very costly for patients and not enough can be made to reach large populations.
  • Novel manufacturing solutions are vital to scalably make existing vectors (esp. AAVs).
  • New vectors which retain the benefits of existing vectors yet can be made inexpensively are also important.
  • Some possible solutions:
    • Synthetic biology methods for radically redesigning cellular platforms of virus production
    • Novel inexpensively manufacturable viral vectors
    • Hybrid nanoparticle-viral vectors that are easier to produce yet retain benefits of viruses and perhaps bring extra advantages as well
    • Methods for production of DNA origami nanorobots
    • Use of DNA origami to support viral capsid assembly and genome packaging

Gene Therapy for Radiation Resistance in Space

  • Extended periods of time in space, on the moon, on Mars, etc. expose people to large amounts of radiation.
  • Future space colonization efforts could be severely jeopardized by human radiation exposure, especially since this can cause problems with reproduction.
  • Some possible genetic approaches:
    • Add genes derived from radiation-resistant organisms (e.g. tardigrades, Deinococcus radiodurans, etc.)
    • Enhance human DNA repair pathways by adding new genetic circuits and/or altering gene regulation
    • Polygenic gene therapy delivery vectors
    • Develop ways of safely delivering genes to most or all cells in the human body

Gene Therapy for Aging

  • Aging affects everyone and is marked by a deterioration of health and eventual death.
  • Treatments for aging would greatly improve the human condition by making people both much healthier and longer lived.
  • Life extension only linearly affects population growth, whereas reproduction exponentially affects population growth, so concerns about life extension causing overpopulation are often exaggerated.
  • As human longevity increases, its small contribution to population growth will likely be mitigated by parallel growth of technologies that improve human sustainability (e.g. vertical farms, cultured meat, renewable energy, space habitation, etc.)
  • Gene therapy has great potential for extending human longevity and simultaneously improving overall global health.
  • Some possible genetic approaches:
    • Polygenic gene therapy delivery vectors
    • Identify multiple genes that synergistically improve healthspan and deliver them together
    • Engineer regulatory pathways and insert genetic circuits that optimally modulate gene expression for improving healthspan

Biological Carbon Capture for Climate Change

  • The climate crisis threatens human and nonhuman life since is leading to desertification, flooding, extreme weather events, ecosystem collapse, etc. and will cause many millions of deaths if it continues unchecked.
  • Addressing climate change will necessitate both policy solutions and technological solutions.
  • Carbon capture is a particularly promising route towards mitigating climate change yet is difficult to scale.
  • Self-replicating biological carbon capture approaches would come with risks but demonstrate much greater scalability.
  • Some possible biological carbon capture solutions:
    • Genetically enhanced trees that more rapidly capture carbon
    • Genetically enhanced cyanobacteria (or algae) that more rapidly capture carbon
    • Bacteriophages that propagate genes in ocean cyanobacteria to enhance their carbon uptake
    • Use bacterial conjugation in ocean cyanobacteria to propagate genes that enhance their resistance to bacteriophages and thus rapidly increase cyanobacterial population size and carbon capture capacity
    • Develop computational models and experimental model systems to explore possible negative side effects of all of the above, find ways to counterbalance those side effects

Strong Nanorobotics

  • Strong nanorobots with capabilities resembling those in science fiction would revolutionize every human activity.
  • Strong nanorobots should specifically possess (1) inexpensive mass producibility or self-replication capabilities, (2) ways of programming them to alter their functionality and environmental responses, (3) automated locomotion oriented towards accomplishing programmed tasks.
  • Only relatively simple nanorobots have been created so far.
  • Some possible routes towards strong nanorobotics:
    • Develop minimal cells derived from Mycoplasma bacteria, equip them with extensive optogenetic equipment for external programming, keep the “programming mode” turned off except when a special chemical switch is flipped to prevent light from scrambling their instructions
    • Synthesize complex dynamic DNA origami nanostructures that include optically programmable logic systems inspired by digital logic circuits as well as automated locomotion modules, also devise scalable manufacturing methods

Horizontal Gene Drives to Repair Pollinator Insect Networks

  • Bees and other insect pollinators form a crucial part of global ecosystems, yet populations of these insects are declining.
  • Decline of insect pollinators is negatively affecting many crops, limiting food production across the world.
  • Some of the most prominent reasons for bee decline are the spread of invasive Varroa mites that carry deformed wing virus (DWV) and the prevalence of toxic pesticides in the environment.
  • Horizontal gene transfer via seeding donor bacteria into insect gut microbiota may help protect insect pollinators in a scalable fashion.
  • Some possible approaches involving horizontal gene drives:
    • Give bees gut bacteria that spread conjugative plasmids carrying anti-Varroa genes.
    • Give bees gut bacteria that spread conjugative plasmids carrying anti-DWV genes.
    • Give bees gut bacteria that spread conjugative plasmids carrying genes that facilitate breakdown of toxic pesticides.

Connectomics Towards Whole-Brain Emulation

  • Mapping the brain and simulating it in a computer would provide an unparalleled holistic understanding of how our minds work.
  • Even partial connectomes and/or animal connectomes could give remarkable insights into neurobiology.
  • The convergence of connectomics and computational neuroscience has applications in bioinspired artificial intelligence, bioinspired robotics, neural prostheses, medicine for brain disease, and more.
  • Some possible routes for connectomics:
    • Expansion microscopy with genetically encoded synaptic and neuronal barcodes coupled with spatial transcriptomics
    • Massively parallel electron microscopy approaches
    • Improved x-ray nanotomography coupled with special sample treatment methods to improve tissue stability, allow multicolor imaging (and possibly barcodes), and enhance resolution
    • Construction of many compact light source devices to rapidly map tissue in parallel
    • Construction of extremely bright next-generation synchrotrons coupled with sample treatment methods to greatly improve stability

Nanobiotechnology for Neural Interfaces and Neural Prostheses

  • Existing neural interfaces and neural prostheses utilize microelectrode-based technologies for communicating with brain tissue.
  • Nanobiotechnology approaches may enable more precise, less invasive, and more powerful neural interfaces and prostheses.
  • Some possible approaches:
    • Polymersome nanocompartments that mimic neurons in their electrical response properties via embedded transmembrane proteins and ion gradients, link to nanowires that transmit electrical potential to external devices or other parts of the brain
    • Leverage gene therapy for modifying human neurons to express optogenetic channels, design nanomachines that incorporate upconversion nanoparticles for targeted stimulation

Terraforming

  • The future of humankind depends on our ability to colonize other planets, moons, etc.
  • Earth is the only planet in the solar system where humans can survive unaided.
  • Terraforming the moon or Mars would provide humankind with a new habitable world, yet this represents an enormously challenging task.
  • Seeding the moon or Mars with heavily engineered microorganisms may provide a first step towards transforming these celestial bodies into habitable worlds.
  • Some possible microorganism-based terraforming methods:
    • Perform extensive metabolic engineering on extremophiles that metabolize substances similar to those found on the moon or Mars, make them convert regolith to Earthlike atmospheric gases
    • Borrow genetic pathways from Deinococcus radiodurans to provide radiation resistance
    • Extensively engineer microorganisms to metabolize regolith and form seaweed-like colonies that bud into edible fruits

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