Prebiotic Membraneless Structures as a way towards Cellurarity

Originally title: Droplets of these simple molecules may have helped kick-start life on Earth from Carmen Drahl ( 

droplets pics

For the origin of life on Earth, ancient puddles or coastlines may have had a major ripple effect.

A new study shows that a simple class of molecules called alpha hydroxy acids forms microdroplets when dried and rewetted, as could have taken place at the edges of water sources. These cell-sized compartments can trap RNA, and can merge and break apart — behavior that could have encouraged inanimate molecules in the primordial soup to give rise to life, researchers report July 22 in the Proceedings of the National Academy of Sciences.

Besides giving clues to how life may have gotten started on the planet, the work might have additional applications in both medicine and the search for extraterrestrial life.

Present-day biology relies on cells to concentrate nutrients and protect genetic information, so many scientists think that compartments could have been important for life to begin. But no one knows whether the first microenclosures on Earth were related to modern cells.

“The early Earth was certainly a messy place chemically,” with nonbiological molecules such as alpha hydroxy acids potentially having roles in the emergence of life alongside biomolecules like RNA and their precursors, says biochemist Tony Jia of Tokyo Institute of Technology’s Earth-Life Science Institute.

Jia’s team focused on mixtures of alpha hydroxy acids, some of which are common in skin-care cosmetics. Though not as prominent as their chemical relatives amino acids, alpha hydroxy acids are plausible players in origin-of-life happenings because they frequently show up in meteorites as well as in experiments mimicking early Earth chemistry.

In 2018, a team led by geochemists Kuhan Chandru of the Earth-Life Science Institute and the National University of Malaysia at Bangi and H. James Cleaves, also of the Earth-Life Science Institute, demonstrated that, just though drying, alpha hydroxy acids form repeating chains of molecules called polymers. In the new study, the pair along with Jia and their colleagues found that rewetting the polymers led to the formation of microdroplets about the same diameter as modern red blood cells or cheek cells.

Prior studies have shown that simple molecules can form droplets(SN: 4/15/17, p. 11).  The new work goes further in showing “that possibly prebiotically relevant molecules can form droplets,” says artificial cell expert Dora Tang of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, who wasn’t involved with the work.

In the lab, the team demonstrated that the droplets could trap and host molecules essential to life as we know it, such as RNA. The researchers also observed that a protein retained its function within the droplets and that fatty acids could assemble around the droplets.

Still, those findings don’t mean the microdroplets were Earth’s first cells or ancestors of them, Chandru cautions. Instead, he suggests that the droplets could have helped reactions along in emerging biochemical systems in the lead-up to the origin of life.

Though the team’s focus is origin-of-life studies, Jia points out that these microdroplets could potentially be engineered to deliver medications. The researchers note in their study that they may apply for a patent related to the work within the next year but have not specified an application.

The new research may also hold an important lesson for the search for extraterrestrial life (SN: 4/30/16, p. 28). “We need to not only focus on detection of modern biomolecules and their precursors, but also other relevant nonbiomolecules” that, like alpha hydroxy acids, might have played supporting roles in the emergence of life, on Earth or elsewhere, Jia says.


Click here for the source article

Click here for Original paper

The missing years (2016-2019)

STEM school



Since 2016, I’ve been busy and didn’t really find the time to blog here. So here is a brief summary of what has happened thus far:

  • Got a couple of papers published:
  • Got appointed at two places:
  • Gave a couple of Science Talks
    • Invited Talk – Faculty of Science and Technology, UKM Bangi, Malaysia (March 2019)- “Mother of all questions- Origins of Life”
    • Invited Talk – University of Duisburg-Essen, North Rhine-Westphalia, Germany (October 2018)- “Using non-standard biomolecules to elucidate the Origins of Life”
    • Contributed Talk  – Interdisciplinary Origins of Life (iOOL) meeting 2018 at Institute for Molecular Evolution, Heinrich-Heine-University, Dusseldorf, Germany, (October 2018) – “The possible role of prebiotic scaffold molecules in the Origins of life ”
    • Contributed Talk  – 18th European Astrobiology Network Association (EANA) conference 2018, Berlin, Germany, (September 2018) – “Combinatorial Chemistry and the Origins of Life: Polyesters”
    • Invited Talk – Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec (BIOCEV), Vestec, Czech Republic (September 2018)- “Scaffolding the Origins of life”
    • Invited Talk- Research Fellows Conference, University of Chemistry and Technology, Prague, Czech Republic (September 2018) “Introduction and Problems in the Origins of Life”
    • Invited Talk – Institute for Planetary Materials (IPM), Okayama University, Misasa, Japan (June 2017)- “Origins of life and its discontent”
    • Invited Talk – NASA Astrobiology Institute’s Thermodynamic, Disequilibrium and Evolution (TDE) Focus Group meeting, ELSI, Tokyo Institute of Technology, Tokyo, Japan, (October 2016) – “The Abiotic Chemistry of Thiolated Acetate Derivatives and the Origin of Life”
  • And some outreach talks in Malaysia (see the attached poster)
    • Public talk at SMK (High School) Wangsa Melawati “How to Find Aliens Vol 2”, 13th March 2019
    • Public talk at Planetarium Negara “How to Find Aliens”, 25th February 2019. 

I will be updating this blog soon with my own OOL stuff.



Setting constraints on origins of life’ hypotheses. Example 1: thioester world and metabolism first in hydrothermal vents

When it comes to origins of life (Ool) hypotheses, we are often served with beautiful stories on how one event follows another and then you get life. But, the devil is always in the details and we want it to be out, to be known and to be addressed.

“Only when negative results are permitted and theories can be abandoned will science  progress in this area (OoL)”

-Robert Shapiro (1935 – 2011)

Here is a summary of my recent paper addressing a weakness in the metabolism first hypotheses in hydrothermal vents.

Thioesters, the prebiotic analogues of Acetyl coenzyme A is a linchpin organic compound in respiration processes in life. Its occurrences have been transposed into geochemical settings such as hydrothermal vents to form many metabolism first schemes for origins of life in the last 40 years or so. One glaring problem, despite the usual poised narration, is that, this hypothesis have survived so long without through investigations for that many years. Now, researchers at Earth-Life Science Institute (ELSI), an institute incepted to exclusively study the origins problem is doing just that, to set constrains on current OoL models and to produce more experimentally driven principles to understand the origins of life.

The open-source paper available in, has demonstrated that the accumulated concentration of thioesters in HT vents are too insignificant to launch any meaningful progression in metabolism first schemes. Additionally, thioester (like Acetyl-Co-A) has a very limited shelf life; the researchers measured the decay rate and concluded that, depending on thioesters speciation and physical conditions, they are unlikely to persist in hydrothermal vent conditions for long, thus constraining the metabolism first hypotheses.

p.s: We are extremely delighted to get this piece out in an open source journal.


Figure is showing the possible formation of thioacetic acids, in blue and thioesters (methyl thioacetic acid) , in pink in hydrothermal vent systems.


Authors: Kuhan Chandru, Alexis Gilbert, Christopher Butch, Masashi Aono and Henderson James Cleaves II

Title: The Abiotic Chemistry of Thiolated Acetate Derivatives and the Origins of Life

Journal: Scientific Reports, 2016

DOI: 10.1038/srep29883


Scribbles on the Gordon Research Conference (2016) for the Origins of Life

January is often a horrendous month for ELSI researchers; first we have our own in-house annual international symposium and then this is followed by our intense internal evaluation seminar, a two-day affair where all ELSI members present their work for the past twelve months. This year I decided to one up that schedule by attending the Gordon Research Conference on the Origins of Life in Galveston, Texas in between these two important events.


This was my first trip to the UNITED STATES OF AMERICA, and I was very excited about it before boarding the flight. After 15 hours of journey, I started to develop mixed feelings about this trip until I was shown to my room at the famously haunted Hotel Galvez (be sure to watch the video in youtube), where I slept for the next 15 hours. That is a personal record.

Here are some of my random observations during the GRC’s intense science program.

  1. You are forbidden to record electronically any of the talks or posters given by the presenters. Because of that very fact, we are ALLOWED to argue aggressively. Rumor has it that there was a legendary argument that took place in the past. When I say argument, I don’t mean light ones. But to my surprise nothing like that happened this time. This was probably because they wasn’t anyone trying to sell/convince you their version of OoL scenario (which usually happens in Origins kind of conferences). This GRC, in my opinion, was amazing since the focus was only in what we know, what we don’t know, and what the current evidence is showing. That was such a relieve for me after witnessing many sales pitches in the field in the past.
  2.  GRC likes placing their conferences in, sorry Galveston, remote areas to create an intimate group setting. This is something that didn’t go well with the enthusiastic foreigner like me who wants to spend some time off as well. But in any case, science always comes first, and I was immensely satisfied with what I have gained (talks and meeting people) and not to mention having the time-off to visit Johnson Space Center with some of my favorite people on board.
  3. The scientific talks were exclusively made for an interdisciplinary crowd, meaning that one never saw a physicist showing only equations and expecting the biologists and chemist to understand, as if it were “matter of fact” knowledge. I don’t mean this in an offensive way but it is really hard to be able to give a talk to an interdisciplinary crowd, something we do almost everyday at ELSI. The GRC Origins was good demonstration of this with few minor exceptions.
  4. The GRC starts from 9 to 12 pm, we then have a huge break until dinner, and talk resumes again from 7.30 to 9.30. This was thoughtful and pleasing as it helps the jet-lagged foreigner to sleep and feel refreshed for the sessions.

One glaring shift I noticed among some of the leading OoL workers in the field is that they are moving away from trying to only understand origins based on modern bio-molecules. This is good news, as we in ELSI are also having similar views and are working to explore new chemical domains within prebiotic chemistries and origins of life. I also noticed that the integration of theory and experiments are also coming into play more than before to understand this complex problem. In my opinion, interdisciplinarity between sciences cannot be forced upon but needs to grow organically. This puts ELSI in an amazing position with all the disciplines combining (sometimes clashing) to solve some of the pieces of the origins puzzle. In my world of complaints and criticisms (I’m an experimentalist), this is one of the best conference I have attended in this field, absolutely worth the jet-lag and crazy ELSI schedule of January.

kuhan2016-01-21 15.58.jpg

originally post on February 4, 2016 (ELSI blog)

38億年の時を 超え、 生体分子生成の瞬間に迫る

Researcher’s Eye 〜地球最大の謎に挑む研究者たち

Kuhan Chandru


kuhan01.jpg「日本での研究はスピードが速くて刺激的。その上、ELSIには第一線の研究者が集まっているから、知りたいことがあればすぐに聞きに行ける。この環境はとても貴重です」と話すのは、ELSI若手研究員 のクーハン・チャンドゥルー。「原始地球で、どのようにして生命誕生につながる生体分子ができたのか」に迫ろうと、自らが中心となって新たな実験を準備中だ。













Original interview appeared on February 2015 ELSI (Japanese) 

Kensei Kobayashi’s flow-reactor, the SCWFR, part 2

The SCWFR at Kensei Kobayashi's lab at Yokohama National University
The SCWFR at Kensei Kobayashi’s lab at Yokohama National University

Kensei Kobayashi’s group with the help of Takeo Kanaeko (a brilliant man) came up with another design where they named it Super Critical Water Flow Reactor (SCWFR) utilizing an infrared (IR) gold image furnace (Figure above). This enables the fluid in this system to heat up to 400 °C (or any desired temperature) within seconds (without pre-heating). This one specification is important as most autoclave and other flow reactors utilized an electrical heater which takes time to heat up to the desired temperature. This is undesirable as this “pre-heating” is also making the initial chemicals to react (or altered) to lower and rising temperature, which is not very realistic to a real vent. In other case, this is one of the slightly more realistic simulators i have worked to date.

Kobayashi’s ex-student, Nazrul Islam performed the survivability experiment using several amino acids (aspartic acid, threonine, serine, sarcosine, glutamic acid, α-aminobutyric acid, β- alanine, γ-aminobutyric acid, 5-aminovaleric acid and 6- aminohexanoic acid), 10 mM each) by heating them up at four different temperatures (250, 300, 350 and 400°C ) at 25 MPa for 2 min (that’s pretty fast). They showed that amino acids tend to show better recovery when it is hydrolyzed, suggesting some kind of aggregation and/or condensation is happening within the system. Additionally they also showed oligomerization of glycine (100mM) with the same temperature. At 400°C, no oligomerization was found. However, at 200-350°C, diketopiperazine, diglycine, triglycine and tetraglycine were formed. It was suggested that the glycine reactions in a supercritical fluid (300°C to 400°C) are quite different from those in the liquid phase (at 200–350°C). There were many other peaks of unknown compounds in all of the chromatograms of the unhydrolyzed products. Most of those peaks disappeared after acid hydrolysis. This particular findings however remains a mystery.

Another of Kensei’s sudent, Hironari Kurihara, used the SCWFR to test the stability of complex compounds produced from simulated primitive atmosphere (similar to Miller and Urey’s work). He then tested these compounds to assess the stability of some known amino acids. The complex-combined amino acids (from the primitive atmosphere simulation) preserved more amino acids (including amino acid precursors that give amino acids after acid hydrolysis) than free amino acids after heating in simulated SHS environments. In other words, these complex chemicals which could come from atmosphere (or space) could be better preserved if they are come into contact with the hot hydrothermal system which could have existed during the prebiotic-earth setting. This also hints that “clean or perfect” chemicals like amino acids used in many kinds of experiments are not necessarily showing the right picture when comes to chemical evolution on early earth. More on this in the future.

Many critics of hydrothermal vent simulators often argues that, simulators mentioned on this post and previous ones have a rather short flow-rate and short flow-length (showing low residence time, meaning how long the sample stays in the system). Critics usually cite studies that refer to residence time of fluids in axial hydrothermal environments range from years to decades, while those in lower temperature off-axis diffuse flow systems may be on the order of thousands of years. The problem with these studies about residential axial time of fluids is that, they’re are based on models and calculation only, no work has been done so far in regards to real time sampling or measuring the length of vent system (although, there are work in measuring the velocity of fluid emitting from a vent which looks promising for future measuring). Despite this limitation, i believe the future of simulators will be done using computer simulators, where experimental data from physical simulators (like the ones mentioned in this blog) could be used as parameters. The biggest advantage in this, is that, we do experiments on a larger scale which is could make the origin of life more complicated, interesting and not so straightforward, which I believe is a good problem to have in the future.

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The flow-reactor, a better hydrothermal vent simulator, part 1

flow-reactor (HCFR) build by Ei-ichi Imai at Nagaoka Institute of Technology.
flow-reactor (HCFR) build by Ei-ichi Imai at Nagaoka Institute of Technology.

In the previous post, i wrote about a conventional kind of submarine hydrothermal simulator (SHS) called the autoclave. In today’s post i will talk about the flow kind of reactor which is more realistic compared to the autoclave. Jack Corliss, the man who discovered a real SHS, came up with the notion that a flow-type reactor is essential for new origin of life experiments, as he argued that the quenching effect of the cold seawater is important to hold the short-lived intermediates (hydrogen cyanide, sugars and etc) or as he calls it “quasi-species” in prebiotic synthesis of bio-molecules. This essentially means that a flow kind of simulators are required to better represent a real SHS to  produce more reliable results than the autoclave.

Initial Schematics of Jack Corliss in his paper
Initial Schematics of Jack Corliss in his paper

Co-incidentally, Koichiro Matsuno, designed a principle idea of a flow reactor which could reflow the fluids repeatedly in heat and cold (i will name here-forth as hydrothermal circulation flow-reactor (HCFR) for convenience). Ei-Ichi Imai, Koichiro Matsuno and co-workers went on to build  (image above, schematics diagram below) the reactor and experimented using many bio-molecules.

Their first paper which made it to Nature (big thing for scientist), reported that oligomerization of glycine could occur at 200-250°C, where a monomer glycine solution was circulating for 2 hours or so. Oligomers up to Hexaglycine was reported when metal (Cu2+) and controlled pH was introduced. Without them, only oligomers up to triglycine could be obtained. They also tried the same experiment using  glycine and alanine. They observed oligomerzation products such as

Schematic diagram of the HCFR system from Nagaoka Institute of Technology
Schematic diagram of the HCFR system from Nagaoka Institute of Technology

diketopiperaxine, gly-ala, ala-gly, gly-ala-ala, ala-ala, ala-ala-ala and ala-ala-ala- ala was created when the solution was heated with similar conditions. What i described abover is a big thing in origin of life studies. This land-mark discovery, was the first to show that oligomerization (a shorter version of polymerization) could occur using basic amino acid (gly), without the help of DNA and RNA molecules which are crucial in making proteins in life.

In their other works, oligomerization of nucleotide up to trimers (basic monomer of DNA) was also observed when 20mM of adenosine monophosphate was used with 1mM ZnCl2 were reflowed at 110°C.

Despite the findings made by HCFR, the system is rather hypothetical, since we know that real live vents don’t really circulate in that manner (shown below) however, this kind of reactor is useful when it comes to monitor chemical changes in the system. In my next post, i will review another kind of flow-reactor in Japan which i have also worked on in the past.

HCFR mimicking a circulatory system in a real life vent.
HCFR mimicking a hypothetical circulatory system in a real life vent.

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Modus operandi in EARTH-LIFE SCIENCE INSTITUTE (ELSI), Japan – Day 0

This article appeared in the ELSI’s blog

1557567_10151911643485911_1948361252_nMay is a month where nothing really happens in Japan. It is the post-sakura season where everyone is done taking pictures of cherry blossoms and is getting ready for a humid and hot summer. I say this with tongue in cheek but there is some truth to the lull of May. People gear up for the new school and fiscal year beginning in April and slowly settle into the pattern of life by May, in relief. I joined ELSI in the beginning of May after going through their multiple interviews in January. Yes, I say multiple interviews to point to the unique way ELSI evaluates its potential newcomer, where you meet numerous people by whom you are not sure you are being judged or just having a scientific exchange. Or both. It is an unconventional way but it seemed to have worked for me much to my delight.

elsiDuring this time, I managed to get to know whom I will be working closely with and I feel lucky to be with people whom are my instant noodle expert (INE). INE are people who will be there to give you suggestions and ideas in an instant. Some of my colleagues may not be here all year long but they are nevertheless very insightful to have around when they are around. Within a few interactions, I realised how much more reading I needed to do and how I can reduce workflows in research. This I got within the first week of being here.

I was also impressed by how collaboration happens here, where fields are interrelated and you get to see the bigger picture. A young scientist often neglects the bigger picture, preferring to dig deeper. At ELSI, the bigger picture is often the talking point and this is how collaborations happen. It is slightly daunting in the beginning but it is exciting once you get it.

Right now I am facilitating in building the chemistry lab, which is almost like a “mansion” room. In Japan, a “one-room mansion” is the common term referring to a studio apartment. This is one of those Japanese terms that I have a hard time comprehending till this day. However, the limits in space will all change, as ELSI will have a new building by the end of next year. For now, we are dealing with making the best of space, which is manageable. Personally, the opportunity of building a lab is an exciting prospect to me, where we are sharing ideas on how to handle the logistics of instruments and materials in a small room. I hope that we will be fully operational by end of summer.

On the lighter note, what I find nice and admittedly a little weird is, the people at ELSI are like a family. We often have lunch together, meet for daily tea-time at 3, and we drink together every Friday. Yes, you could surmise that perhaps we don’t have many friends. However, friendless or not, some of the best discussions happen here. It is like a mix of getting to know some of the research staff and building a connection between them. We are planning to watch some of the World Cup matches together. My general advice is, don’t mix work and life together. But ELSI is an exception, I suppose.

Finally, I would like to convey my appreciation to the wonderful set of support staff we have at ELSI. They have made my registrations and other legal obligations amazingly easy since day 1. Moreover, they are always welcoming when you approach them in their office. They make a point to ask you personal questions (the nice ones), to be your friend and to make your time here a smooth one.

All is pretty good, until of course we find ourselves rooting for opposing teams when we watch the World Cup matches together as an ELSI family!