During my pursuits, I’ve come across an increasing number of exciting nontraditional routes for funding scientific research. The efforts of Adam Marblestone and Benjamin Reinhardt have been particularly instrumental in stimulating this ecosystem, but many other great people have contributed as well. These new funding routes are a welcome relief since many of the most innovative and far-reaching projects are not especially suited for receiving governmental NIH, NSF, etc. funding. If you would like to find a more comprehensive list of such alternative funding sources, you should check out https://arbesman.net/overedge/. My own list (below) consists of funding sources that stand out to me as particularly promising. I hope you find this useful and feel free to reach out if you have any questions!

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Amaranthe Foundation https://amaranth.foundation/bottlenecks-of-aging “We outline initiatives which, if executed, could meaningfully accelerate the advancement of aging science and other life-extending technologies. The resulting document is a philanthropic menu, for which Amaranth is seeking both talent to execute on and co-funders. If you are a founder, researcher, or philanthropist interested in executing or co-sponsoring one or several of the projects or proposals below, please reach out to us”

An excellent and inspiring writeup of the story of Dyno Therapeutics, one of the most exciting startups in the gene therapy world.

How AI can accelerate gene therapy.

An amazing graph theoretic analysis of the C. elegans neuropeptide connectome!

Neuromodulation by peptides is essential for brain function. By comprehensively mapping neuropeptide signaling in the nematode C. elegans, Ripoll-Sánchez et al. define a dense wireless network whose organization differs in important ways from wired brain circuits. This network is a prototype for understanding neuropeptide signaling networks in larger brains.

An excellent short review on structure and function of the hypothalamus, one of my favorite regions of the brain! Link: https://www.science.org/doi/10.1126/science.adh8488 #neuroscience #biology

The hypothalamus (“hypo” meaning below, and “thalamus” meaning bed) consists of regulatory circuits that support basic life functions that ensure survival. Sitting at the interface between peripheral, environmental, and neural inputs, the hypothalamus integrates these sensory inputs to influence a range of physiologies and behaviors. Unlike the neocortex, in which a stereotyped cytoarchitecture mediates complex functions across a comparatively small number of neuronal fates, the hypothalamus comprises upwards of thousands of distinct cell types that form redundant yet functionally discrete circuits. With single-cell RNA sequencing studies revealing further cellular heterogeneity and modern photonic tools enabling high-resolution dissection of complex circuitry, a new era of hypothalamic mapping has begun. Here, we provide a general overview of mammalian hypothalamic organization, development, and connectivity to help welcome newcomers into this exciting field.

Stupendous paper on a new spatial transcriptomic atlas of mouse brain by Shi et al. from Xiao Wang’s group at MIT. They leverage their in situ sequencing method “STARmap PLUS” to profile 1,022 genes in 3D and map 1.09 million cells across the adult mouse brain and spinal cord. While they did not use the whole brain, instead opting for a series of thick sections at regular intervals, they still covered a lot of ground! Furthermore, they employed graph-theoretic computational methods to predict wider gene expression profiles of cells in their dataset, imputing single-cell expression profiles of 11,844 genes. This dataset/resource will serve the neurobiology community in elucidating the mechanistic workings of the brain!

In situ spatial transcriptomic analysis of more than 1 million cells are used to create a 200-nm-resolution spatial molecular atlas of the adult mouse central nervous system and identify previously unknown tissue architectures.

Neurotechnology will improve our lives in many ways. However, to sustain a world where our neurobiological data (in some cases perhaps including our innermost thoughts and feelings) remains properly secure, we must invest in both policy and technology that prevents bad actors from stealing private information or even directly manipulating people’s brains. We don’t want the very real possibility of ‘telepathy’ and ‘mind control’ to harm people and society. So, let’s start laying the groundwork now to ensure the best possible neurotech future! #neurotech #future #policy #neuroscience

We provide a Perspective highlighting the significant ethical implications of the use of fast-developing neurotechnologies in humans, as well as the regulatory frameworks and guidelines needed to protect neurodata and mental privacy.

Fascinating 3D electron microscopy study by Parlakgül et al. wherein they compare the subcellular organization of liver tissue from lean and obese mice. The authors found substantial differences in endoplasmic reticulum (ER) organization. These ER differences were shown to directly influence metabolic health in a causal fashion, opening the doors to new ways of treating metabolic dysfunction. #electronmicroscopy #cellbiology #metabolism

Detailed reconstruction using enhanced focused ion beam scanning electron microscopy imaging and deep-learning-based automated segmentation demonstrates that hepatocyte subcellular organelle architecture regulates metabolism.

An extremely important landmark paper by Watson et al. from David Baker’s group. They developed RFdiffusion, a generative AI for protein engineering. With this tool, scientists can generate new protein designs. The software can generate novel monomers, multimers, and symmetric protein cages. It can generate proteins that bind to desired targets as well as enzymes that position active sites at a desired location on the structure. I would say that this technology has the potential to dramatically alter how biology and biotechnology is done. I’ve been waiting for something like this since middle school! So exciting to see protein engineering reaching this point!! #computationalbiology #proteinengineering #syntheticbiology #biotechnology #biochemistry #ai #generativeai

Fine-tuning the RoseTTAFold structure prediction network on protein structure denoising tasks yields a generative model for protein design that achieves outstanding performance on a wide range of protein structure and function design challenges.

General-purpose automation could radically improve society by vastly accelerating construction, manufacturing, and R&D. Just as the scale and complexity of today’s cities would have been unimaginable 200 years ago, we may see a similar factor of value growth over the next 50 years. Quality of life may dramatically increase as well. I envision that billions could be lifted out of poverty and the average person may live like today’s wealthiest top 1%. Space colonization might be made feasible. Keep in mind these projections are highly speculative. Nonetheless, it is worth considering the remarkable possibilities! #automation #tech #robotics #futurism

The rise of humanoid robots didn’t happen overnight, but a kind of perfect storm has accelerated the phenomenon over the past year and change. The foundation, of course, is decades of research.

Toiling away in research facilities and R&D departments laid the ground work for a new generation of technology. The necessary software and components have come a long way, driven by innovations in industrial robotics, autonomous driving and even the smartphone industry.

And then a global pandemic happened. The events of the last few years have been important for two deeply interconnected reasons. First, investment in robotics has skyrocketed. Second, staffing continues to be an issue. You could say that these conditions have created a humanoid-shaped hole that a robot could walk right through.

Cool paper that adds a useful tool to the gene therapist’s toolbox! Young et al. utilize an in vivo screening method to develop adeno-associated viruses (AAVs) which target microglia. They show that their AAVs transduce central nervous system microglia as well as tissue macrophages after intravenous injection. #biotechnology

Tissue macrophages, including microglia, are notoriously resistant to genetic manipulation. Here, we report the creation of Adeno-associated viruses (AAV) variants that efficiently and widely transduce microglia and tissue macrophages in vivo following intravenous delivery, with transgene expression of up to 80%. We use this technology to demonstrate manipulation of microglia gene expression and microglial ablation, thereby providing invaluable research tools for the study of these important cells.