Challenges of Particular Interest to Me

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 centers on helping people and on protecting the future of the human species. I am therefore interested in a wide array of contemporary challenges. As a synthetic biologist, I can capitalize on my field’s multidisciplinary nature to explore many distinct applications. It should be noted that, as just one person, my knowledge can only go so deep in so many areas. Furthermore, interdisciplinary projects are much more likely to succeed when experts from multiple fields work together. Because of this, I extensively leverage collaboration. 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 creating a bright future. I chose the featured image of a Martian-hued rendering of a group of Anasazi cliff dwellings 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.

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 doses can be made to reach large populations. Novel manufacturing solutions are vital to scalably make existing vectors (esp. AAVs). I am also particularly interested in developing new types of vectors that can be manufactured inexpensively while still retaining the benefits of existing delivery systems. Here are some potential directions of interest.

• Synthetic biology methods for radically redesign of cellular platforms of virus production
• Novel inexpensively producible viral vectors.
• Hybrid nanoparticle-viral vectors that are easier to produce yet retain benefits of viruses (and perhaps feature additional advantages).
• Methods for production of DNA origami nanorobots.
• DNA origami tools to support viral capsid assembly and genome packaging, methods for making these tools cheaply enough to facilitate their purpose.

Antibacterial Resistance

In particular, I hope to combat high risk pathogens such as carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter, Clostridioides difficile, and drug-resistant Neisseria gonorrhoeae. Adaptability and rapid generation of new solutions will represent key qualities to keep up with resistance. Here are some potential directions of interest.

• Treatments based on engineered bacteria to combat the pathogenic bacteria.
• Rational design (nanobiotechnology focus) of phage therapies.
• Phage therapy production platforms for rapid generation of diverse therapeutic candidates
• 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.
• Gene therapies which enhance the immune system to combat antibiotic resistant bacteria.
• Rapid inexpensive biomanufacturing tools for making vaccines, rapid vaccine discovery platforms.
• Affordable home diagnostics.

Biological Carbon Capture for Climate Change

The climate crisis threatens human and nonhuman life. Some of the detrimental effects of climate change are desertification, flooding, extreme weather events, ecosystem collapse, food shortages, and emergence of new pathogens. As a result, climate change will cause many millions of deaths if it continues unchecked. It should be noted that addressing climate change will necessitate both policy changes and technological solutions. Carbon capture represents a particularly promising route towards mitigating climate change yet is difficult to scale. Self-replicating biological carbon capture approaches should display much greater scalability, though they will come with risks that must be addressed prior to deployment. Here are some potential directions of interest.

• Develop genetically enhanced trees that more rapidly capture carbon.
• Develop genetically enhanced cyanobacteria (or algae) that more rapidly capture carbon.
• Design bacteriophage-based delivery systems to propagate genes in ocean cyanobacteria to enhance their carbon uptake.
• Engineer bacterial conjugation delivery systems in ocean cyanobacteria to propagate genes that enhance resistance to bacteriophages, thus rapidly increasing cyanobacterial population size and carbon capture capacity (this would require carefully balanced implementation to avoid unintended negative side effects).
• Develop computational models and experimental model systems to explore possible side effects of all of the above, find ways to counterbalance those side effects.

Connectomics Towards Whole-Brain Emulation

Mapping the human brain (connectomics) at nanoscale resolution would enable a series of unprecedented advances across basic and applied neuroscience. Connectomics has potential applications in bioinspired artificial intelligence, bioinspired robotics, neural protheses and brain-computer interfaces, and treatments for brain disease. Connectomes may also provide the foundational first step towards whole-brain emulation; that is, simulation of the mind (and body) in a computer with sufficient biological realism to accurately recapitulate behavior. Whole-brain emulation has applications as a platform for studying brain function and brain disease (but note that are possible ethical concerns around such platforms), as one of the necessary steps towards gradual replacement mind uploading, as a way of recreating the human mind in a nonbiological body to facilitate space colonization, and more. Here are some potential directions of interest.

• Synchrotron expansion x-ray microscopy as a route to mapping mammalian connectomes in reasonable timeframes (i.e. a few years of imaging as opposed to thousands or millions of years of imaging).
• Improved x-ray microscopy hardware along with new sample treatment methods to improve tissue stability as well as allow multicolor imaging and possibly barcodes for labeling.
• Construction of many compact light source devices to efficiently map brain tissue in parallel.

Gene Therapy for Aging

Aging affects everyone. It is marked by deterioration of health and eventual death. Treatments for aging would greatly improve the human condition by making people both healthier and longer lived. It should be noted that 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. Here are some potential directions of interest.

• Develop multigenic gene delivery vectors to facilitate complex genetic interventions towards mitigating aging in the brain and elsewhere.
• Design tools to identify how multiple genetic changes may synergistically improve healthspan and longevity, develop gene therapies that implement these changes together.
• Engineer regulatory pathways by inserting genetic circuit loci which optimally modulate gene expression for improving healthspan and longevity.

Gene Therapy for Space Colonization

Extended periods of time in space, on the moon, on Mars, etc. expose astronauts to large amounts of radiation. Furthermore, this represents just one example of the many physiological issues encountered as a consequence of prolonged time in space. Future space colonization efforts could be severely jeopardized by human radiation exposure and other physiological issues. An important specific problem is that radiation can cause problems with human reproduction, which may hamper efforts to populate the moon and Mars. Here are some potential directions of interest.

• Insert genes derived from radiation-resistant organisms such as tardigrades and Deinococcus radiodurans.
• Enhance human DNA repair pathways by adding new genetic circuits and/or by altering gene regulation to bias towards repair.
• Design tools for studying how genetic changes influence bone tissue responses to microgravity.
• Develop multigenic gene delivery vectors to facilitate complex genetic interventions towards improving physiological responses to space.
• Develop delivery systems that can safely transduce most or all cells in the adult human body.

Horizontal Gene Drives to Repair Pollinator Insect Networks

Insect pollinators form a crucial part of global ecosystems, yet populations of these insects are declining. In particular, many species of bees contribute heavily to ecosystem health via pollination. Decline of insect populations is furthermore negatively affecting many crops, limiting food production across the world. Some of the more prominent factors specifically causing bee decline include spread of invasive Varroa mites that carry pathogens like the deformed wing virus and prevalence of toxic pesticides in the environment. Here are some potential directions of interest.

• Horizontal gene transfer could occur after seeding donor bacteria into insect gut microbiota may help protect insect pollinators in a scalable fashion.
• Developing engineered gut bacteria with conjugative plasmids which propagate genes to combat Varroa mites, genes to combat deformed wing virus, and/or genes to degrade pesticide toxins could help mitigate bee decline.

Infectious Disease Burden in Developing Countries

As ailments which cause some of the most widespread suffering, I am especially interested in combatting malaria, tuberculosis, and HIV. I hope to implement translational strategies for dissemination of solutions. Here are some potential directions of interest.

• 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.

Nanobiotechnology for Neural Interfaces and Neural Prostheses

Existing neural interfaces and neural prostheses mostly use microelectrode-based technologies for recording and stimulating neuronal tissues. But microelectrodes are invasive, usually cause inflammation and glial scarring, and lack spatial precision. Nanobiotechnology approaches may allow less invasive, less toxic, and more precise neural interfaces and prostheses. Here are some potential directions of interest.

• Polymersome (or similar) compartments which mimic neurons in their electrical response properties using embedded transmembrane proteins.
• Such compartments may transmit current along protein-based nanowires to external devices or to other parts of the brain.
• Develop gene therapies to deliver DNA encoding ultrasound-responsive ion channels, enabling spatially controllable neurostimulation
• Develop delivery system to transport gas vesicles into the brain, allowing spatial ultrasound activation of cargo release for drug or gene delivery. This may also have applications to certain kinds of neural interfaces.

Nanorobotics

Researchers have so far created only simple nanorobots. More advanced forms of nanotechnology would enable a wide range of new directions across medicine, manufacturing, agriculture, space, and more. Ideally, stronger nanorobots should possess (1) inexpensive mass producibility or self-replication capabilities, (2) ways of programming them to alter their responses to stimuli, and (3) automated locomotion. Here are some potential directions of interest.

• Develop highly programmable microorganism-based nanorobots, perhaps using a combination of minimal cell technology (make sure to minimize immunogenicity as part of this) and complex optogenetic systems to facilitate external programmability.
• Design dynamic DNA origami nanostructures which incorporate optically programmable logic systems inspired by digital circuits.
• Develop scalable manufacturing platforms for new nanorobotics designs.

Terraforming

The future of humankind depends on space colonization, yet Earth represents the only planet in our solar system where humans can survive unaided. Terraforming the moon and/or Mars would provide us with new habitable worlds. Unfortunately, terraforming these places will be an enormously difficult task. Here are some potential directions of interest.

• Seeding Mars with heavily engineered extremophile microorganisms might act as a first step towards creating a new habitable world. They could metabolize regolith and convert it to Earthlike atmospheric gases and other useful substances.
• A similar approach might work on the moon, but it would be much more difficult due to the even harsher environment and complete lack of atmosphere.
• Certain types of nanoparticles may facilitate atmospheric warming on Mars, so developing ways of further augmenting the effects of such nanoparticles may benefit terraforming efforts.
• Develop ways of extensively engineering mosslike microorganisms so that they grow directly on partially terraformed Mars or moon may provide an abundant food source for early colonists. With the vast amount of land available, it may even be possible to send such food back to Earth to ameliorate world hunger.