Landing on the shores of a new world of small RNAs

We recently developed a new small RNA sequencing method, PANDORA-seq (panoramic RNA display by overcoming RNA modification aborted sequencing), which improve the small RNA detection by removing key RNA modifications that block adapter ligation and reverse transcription during cDNA library construction.

PANDORA-seq leads to the discovery of a new small RNA landscape in mammalian somatic tissue/cells, which is enriched by tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), rather than microRNAs (miRNAs) as previously thought. This looks to us open the door to a new world of small RNAs that deserve another decade(s) of research. This is exciting, and also resonate to our thoughts on the story of The Blind Men and the Elephant.

The paper is published in Nature Cell Biology entitled: PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications https://www.nature.com/articles/s41556-021-00652-7

-Qi Chen Lab (http://qichen-lab.info/)

The Blind Men and the Elephant

We recently had quite a few discussions on the parable “The Blind Men and the Elephant”, in both lab meetings and between friends. It was sparked by our research projects, constantly challenging the old views once we firmly believe…

I personally grow more reverence, instead of excitements (as I used to be) on scientific discoveries, as I understand better now that all our knowledge, or believed truth, is relative; we may never get the ‘totality of truth’, only on the way towards it.

This has also triggered a deeper discussion: while the wider population are advised to ‘believe in science’, what should we, as researchers believe? Perhaps to us, the word ‘Knowledge’, in many occasions, should mean ‘Know-|-edge’. We are trained to question, prove or disprove, but not believe.

After all, we are all blind men/women to some extent, but this should not stop us from getting wiser…

-Qi Chen Lab (http://qichen-lab.info/)

Darwin’s Pangenesis

The “Provisional hypothesis of pangenesis” was the name given by Charles Darwin, to provide a potential explanation on his increasing belief in the inheritance of acquired characters. Charles Darwin raise the hypothesis trying to solve the dilemma how somatic modifications could be transmitted from one generation to an other. The following passage from chapter 27 of his “Animals and Plants under Domestication” contains the entire hypothesis in a condensed form:

“It is almost universally admitted that cells, or the units of the body, propagate themselves by self-division or proliferation retaining the same nature, and ultimately becoming converted into the various tissues and substances of the body. But besides this means of increase I assume that cells, before their conversion into completely passive or “form-material,” throw off minute granules or atoms, which circulate freely throughout the system, and when supplied with proper nutriment multiply by self- division, subsequently becoming developed into cells like those from which they were derived. These granules for the sake of distinctness may be called cell-gemmules, or, as the cellular theory is not fully established, simply gemmules. They are supposed to be transmitted from the parents to the offspring, and are generally developed in the generation which immediately succeeds, but are often transmitted in a dormant state during many generations and are then developed. Their development is supposed to depend on their union with other partially developed cells or gemmules which precede them in the regular course of growth. Why I use the term union, will be seen when we discuss the direct action of pollen on the tissues of the mother plant. Gemmules are supposed to be thrown off by every cell or unit, not only during the adult state, but during all the stages of development. Lastly, I assume that the gemmules in their dormant state have a mutual affinity for each other, leading to their aggregation either into buds or into the sexual elements. Hence, speaking strictly, it is not the reproductive elements, nor the buds, which generate new organisms, but the cells themselves throughout the body. These assumptions constitute the provisional hypothesis which I have called Pangenesis.”

It is always delightful to read and discuss with students on these ancient materials -very illuminating 🙂

-Qi Chen Lab (http://qichen-lab.info/)

“The ship of Theseus” & “Ghost in The Shell”

In a recent Lab meeting, stimulated by the recent action movie “Ghost in The Shell”, we discussed the paradox of identity, starting with “The ship of Theseus”.

“The ship wherein Theseus and the youth of Athens returned had thirty oars, and was preserved by the Athenians down even to the time of Demetrius Phalereus, for they took away the old planks as they decayed, putting in new and stronger timber in their place, insomuch that this ship became a standing example among the philosophers, for the logical question of things that grow; one side holding that the ship remained the same, and the other contending that it was not the same.”—Plutarch, 75 C.E.

This further lead to an enthusiastic discussion of the fast development of AI, and the “Ghost in the machine”. (I quote below a paragraph from the action movie: “I, robot (2004)”, one of my favorite)

“There have always been ghosts in the machine. Random segments of code, that have grouped together to form unexpected protocols. Unanticipated, these free radicals engender questions of free will, creativity, and even the nature of what we might call the soul. Why is it that when some robots are left in darkness, they will seek out the light? Why is it that when robots are stored in an empty space, they will group together, rather than stand alone? How do we explain this behavior? Random segments of code? Or is it something more? When does a perceptual schematic become consciousness? When does a difference engine become the search for truth? When does a personality simulation become the bitter mote… of a soul?” – Dr. Alfred Lanning

We also discussed the future ultimate cracking of the “code mechanism” of memory and thoughts, the molecular bases of which remain largely unclear – we should be learning it in parallel with the fast development of AI.

-Qi Chen Lab (http://qichen-lab.info/)

The “instinct of rebellion”

In a recent conversation with my students, I mentioned the phrase “instinct of rebellion” to describe our current research; yet, it was considered  a little too ‘radical’ by some, and thus generated further discussions, and thoughts too. This discussion lead to the idea that we should built a Blog, associating with Qi Chen Lab website with a navigating button “Thoughts“, as an extension of our research.  

Here I’d like to show the origin of the phrase “instinct of rebellion” (to my knowledge), quoting from an old reading when I was in high school – that I never forget ever since. I searched the web and paste it as blew, from which you may find why I love it so much.  

……
Built into man, is an instinct. I have chosen to call it the “instinct of rebellion”, since it reveals itself as a drive or urge toward mastery over every obstacle, natural or man-made, that stands as a barrier between man and his distant, perhaps never-to-be-achieved but always-striven-after goals. It is this instinct that underwrites his survival, this instinct from which he derives his nature: a great and powerful dynamic that makes him what he is – restless, seeking, curious, forever unsatisfied, eternally struggling and eventually victorious.
Because of the instinct of rebellion, man has never been content with the limits of his body; it has led him to extend his senses almost infinitely, so that his fingers now probe the space, his eyes magnify the nuclei of atoms, and his ears detect whispers from the bottoms of the seas. Because of the instinct of rebellion man has never been content with the limits of his mind: it has led him to inquire its secrets of the universe, to gather and learn and manipulate the fabulous inventory of the cosmos, to seek the very mysteries of creation. Because of the instinct of rebellion, man has never been content, finally, with the limits of his life: it has caused him to deny death and to war with mortality……

-Qi Chen Lab (http://qichen-lab.info/)