Research readings

Insights into variation in meiosis from 31,228 human sperm genomes

• Development of Sperm-seq to study meiosis by sequencing human sperm genomes with single cell resolution
• Number of crossovers likely dictated by nucleus-wife factor
• More crossovers further from centromere; regions closer to centromere utilised much more for people with overall higher crossover rates
• “...crossover-location and crossover-spacing phenotypes reflect underlying biological factors that vary from person to person”
• Aneuploidy: more chromosome loss than chromosome gain
• Lack of correlation between errors from meiosis I and II within individuals and chromosomes -> different vulnerabilities
• The role of sleep may be to regulate the ancient biochemical process of oxidation across the entire body, not just the brain— as evidenced by rising levels of ROS in guts of sleep-deprived flies and mice.
• A new approach to animal tracking, ICARUS, is now utilising smaller, more cost-effective tags detected by the ISS. Scientists hope to integrate this higher-resolution data with existing databases and track both more individuals and species.
• Technological innovations have historically come from individuals experimenting in the “gray zone”between normal operations and unethical activities. However, the gray zone for the current state of intelligent technologies is shrinking, with more people turning to more and more risky, highly visible options with little chance to learn from mistakes— single experts have more control over procedures and thus there is less opportunity for stepwise learning by trainees. To promote more productive adaptation of new tech, ask yourself the following... 1) Can you practice surveillance restraint? 2) What new tactics do you need to find innovation? 3) How can you use intelligent tech to help?
• How can the oceans help us “save” the climate? Offshore wind... Carbon sequestration through marine ecosystems (“blue carbon”)... Algae biofuels... Regenerative ocean farming...
• Our brains really, really like telling stories. Science has the potential to clarify false narratives we tell ourselves, but only if we move past the story trap in the practice of science itself.
• How can free will really exist if everything, including the cellular mechanisms behind neural networks in our brains are fundamentally dictated by the Schrödinger equation? Because everything is also dictated by constraints, like initial conditions, and there simply is no possibility of ever knowing the initial state of the entire universe. Or something like that.
• An overview of the cool new methods and tech people are using toculture and identify previously undiscovered microbes...
• The story of how Manu Prakash (at Stanford, who invented the Foldoscope!) is trying to capture & study one of the world’s simplest animals, the Trichoplax adhaerens, which lies at the transition point of unicellular to multicellular life (an example of “active matter,” with loosely coordinated cells). Studying this creature’s behaviours can teach us about the origins of multicellularity, brains, cancer... and even its physical properties, an odd mix of solid and liquid are intriguing.
• Recent years have seen a “tsunami” of data gathered on the oceans, especially through autonomous vehicles. However, several barriers stand in the way of optimal utilisation of the new information: silos and desire for control preventing sharing of data between organisations; inconsistent data formats and quality; and fragmentation of datasets, communities, and norms. Possible solutions? Federated networks of existing data sets by establishing standards and protocols for collection; open data as the new default; business innovations to support data collection and management, as well as to incentivise supply chain transparency
• An interesting glance into the science of seasickness... Perhaps triggered by the same toxin system that responds to poisons with nausea?

Responsiveness to perturbations is a hallmark of transcription factors that maintain cell identity

• Transcription factors can act as lineage maintainers and/or establishers... not necessarily the same!
• Two options for how TFs important for lineage maintenance can respond to perturbation: as pillars (stay expressed to the same degree as a constant marker) or as springs (being upregulated to maintain homeostasis).
• Came up with P^3 approach to identify transcriptome-wide responses to perturbations (75 small molecule combos), first in iPSC-derives cardiac myocytes
• Identified many responsive genes, which comprised a superset of known lineage-specific genes
• Lineage-maintaining TFs acted as springs (highly responsive!); not necessarily cell-type specific, so may act in general homeostatic feedback loops to maintain cell identity
• Knockdowns of these factors made cells (dermal fibroblasts, this time) easier to reprogram

Long-term association of a transcription factor with its chromatin binding site can stabilize gene expression and cell fate commitment

• Most TFs thought to occupy binding site for brief periods of time in oscillatory patterns...
• Using Xenopus oocytes and Firefly & Renilla reporters, showed that certain TFs (Asl1, a nerve-inducing factor) actually bind for long periods of time (hours) and are not displaced by competition
• Also showed this for estrogen receptor!
• Just like participants in human psychology studies have been shown to be more WEIRD— that is, white, educated, industrialised, rich, and democratic— than the average person, subjects in animal psychology studies are often biased on the factors described by STRANGE: social background; trappability and self-selection; rearing history; acclimation and habituation; natural changes in responsiveness; genetic make-up; and experience.
• A look into the science of synesthesia, including potential genetic links related to axon development and the parietal cortex, the association center of the brain.
• A theory of how consciousness may be an intrinsic property of matter,analogous to space-time— so everything has consciousness (for example, the reaction of plants to light, or the spin of an electron) and what we regard as our consciousness is actually more of an illusion of self. Or something like that.

Chromatin potential identified by shared single cell profiling of RNA and chromatin

• Buenrostro/Regev collab
• Developed method (SHARE-Seq) to simultaneously sequence chromosome accessibility and transcriptome in single cells
• Found that changes to epigenone can “foreshadow” changes in cell state— priming? Can identify trajectories like in RNA velocity, but with chromatin potential
• Can identify cell types that are characterised by either epigenome or transcriptome individually at higher resolution because combinatorial
• The state of things regarding extracellular RNA— which is much more existent and potentially impactful than we initially thought!
• Some proteins and other biomolecules in cells undergo “phase separation,”forming droplets like oil in water. Recently, many drugs have been found to concentrate in certain droplets, which can concentrate or dilute them, thus influencing their effect.
• Interesting carbon capture idea, involving spreading a volcanic mineral called olivine over beaches to accelerate a natural drawdown process of the global carbon cycle.
• The clever, random, creative, and useless “hacks”people are coming up with in urban settings in response to coronavirus.
• Insights into the impossible conflict between expectations of being a productive worker and great parent.
• People are working to engineer the oil palm to have a higher yield, in order to limit deforestation... because just banning it could actually exasperate the problem.

Mapping genetic effects on cellular phenotypes with “cell villages”

• Census-Seq: analogous to pooled CRISPR screens but using cells from different human donors instead of gRNA library; combine into “villages,” then sort on phenotype and see how composition changes —> what genetic variants contribute to a certain phenotype?
• Also developed algorithms Roll Call and CSI to identify the presence of unexpected donor cells with known genomes or unknown genomes respectively; also helpful for cell line validation
• Protocols to help deal with different growth rates
• Advantage = can query oligogenic diseases, maybe even polygenic diseases; also looks at how RNA level affects protein expression

Books

• The Body — Bill Bryson — 6/5/20
  • An enjoyable collection of anecdotes on the human body, how the science of it unravelled over history, and how it relates to our societal context. Recommend!
• Private Citizens — Tony Tulathimutte — 6/6/20
  • Weird and not quite interesting enough to make up for it.
• The History of Bees — Maja Lunde — 6/7/20
  • Was okay. Interesting concept, but a bit slow, and the intertwining of the three narratives was anticlimactic.
• Life Finds a Way — Andreas Wagner — 6/12/20
  • What Evolution Teaches Us About Creativity
  • Draws analogies between how evolution occurs as a balance between genetic drift, which introduces variation, and natural selection, which directs change, and the creative processes of humans as a balance between generative/divergent thinking (daydreaming, random associations, etc.) and convergent thinking (being mindful, more conservative?), and even between natural, physical processes like the formation of molecules, where temperature introduces variation and thermodynamic stability finds the minimum energy
  • All the above involve rugged landscapes, where it would be easy to get stuck in local minima or on local maxima without the creative or random factor to bounce things around
• What a Fish Knows — Jonathan Balcombe — 6/13/20
  • Learned that fish are a hell of a lot more interesting than I ever knew! They are more biologically, behaviourally, and
• The Song of Achilles — Madeline Miller — 6/14/20
  • Heartbreaking, and so emotionally engaging. 10/10!
• Kudos — Rachel Cusk — 6/18/20
  • Was okay. Some interesting observations raised on the human condition, and new— but not particularly enthralling.
• The Quantum and the Lotus — Matthieu Ricard & Trina Xuân Thuân
  • How do Buddhist thought and the current scientific view regarding the origins of the universe, consciousness, etc. compare? They’re surprisingly comparable, and Buddhism’s concept of the true emptiness of the universe is an interesting take on the fundamental theory of reality.
  • Also, the idea that science alone is value neutral— only in combination with a system of ethics can it be used to reduce human suffering.
  • Lots more that I’ll try to type up soon!

Vocab

• Rara avis: a rare person or thing, rarity; literally, Latin for a rare bird
• Ne plus ultra: literally, Latin for “no more beyond;” the most perfect example; ultimate
• Peripatetic: travelling from place to place, in particular working or based in various places for relatively short periods of time; Aristotelian
• Beatific: feeling or expressing blissful happiness; rapturous; blessed
• Je ne sais quoi: French for “I do not know what,” used to capture an indescribable, special distinguishing feature, or to name some unnamable quality
• Coruscating: flashing or sparkling; severely critical, scathing
• Inculcate: instill or teach an idea, attitude, or habit by persistent instruction
• Puissance: great power, influence, or prowess; or a competitive test of a horse’s ability to jump large obstacles in showjumping
• Genuflecting: lower one’s body briefly by bending one knee to the ground, typically in worship or as a sign of respect