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

Posted on by Kuhan Chandru

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 Sci.report, 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.

Dropbox

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

Reference

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

Posted on by Kuhan Chandru

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.

grcphoto_2016_origins-(1)-1.jpg

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

Posted on by Kuhan Chandru

Researcher’s Eye　〜地球最大の謎に挑む研究者たち

Kuhan Chandru

生命誕生に迫るという大きな目標を見据えて

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。
母国はマレーシア。海に囲まれたこの国で、大学生の頃には海洋環境の研究に携わっていた。しかし、海でサンプルを採取して分析するという日々の繰り返しに、当時は面白さを見いだせなかったという。転機となったのは、2010年に来日し研究分野を変更、横浜国立大学の小林憲正教授の下で、アミノ酸や核酸、糖など生き物を形づくっている生体分子がどのようにしてできたのかを探る研究に携わるようにったことだった。そして2014年5月、小林教授の勧めもあってELSIの研究員公募に応募した。
「以前、研究を面白く感じられなかったのは、研究の全体像を理解していなかったからだと思う」と振り返る。そして今”生命の誕生に迫る”という大きな目標を見据えながら、生体分子の研究を進めている。

本当のところはわかっていない、生体分子の生成

チャンドゥルーが興味をもつ生体分子に関する研究は、現状どうなっているのだろうか。生体分子の生成といえば、1953年に行われたユーリー・ミラーの実験が有名である。水素やメタン、アンモニアを含む気体を原始大気に見立て、そこに雷に見立てた電気的な放電を行ったところ、生体分子の1つであるアミノ酸が合成された。この実験は「原始の地球で生体分子が発生する可能性が十分ある」ことを初めて示した点で重要であった。しかし、これが実際に地球で起こったのかどうか、さらに生命誕生につながったのかどうかは、未だに明らかになっていない。そのため、「実際にどんな生体分子の生成が生命誕生につながったのか」を突き止めようと、多くの学者による研究や調査が続いている。
生体分子ができるためには、陸地の岩石が反応触媒として働き、落雷や紫外線、火山噴火の熱などのエネルギー源が必要であるという理由から、”浅い海”が長らく生体分子生成の有力地とされてきた。それが1970年代に入ると、海底の熱水噴出孔が注目されるようになった（図1）。西オーストラリアのバクテリア化石の調査から、「初期の生命体は陸から遠く離れた遠洋域に生育していた」とされ、陸から離れた場所で生体分子ができる可能性がある場所として、熱水噴出孔が有力な候補の1つになったからだ。
「しかし、これらはいずれも状況証拠に基づく仮説です。現実に一歩近づくためには、実験で確かめる必要がありますが、これまでには十分な実験が行われていません」とチャンドゥルーは自らがこれから行おうとしている実験の意味について話す。

図1.jpg図1：チャンドゥルーは、海底の熱水噴出孔やマグマが流れ込む海岸付近、落雷地点など温度変化（エネルギー供給）の見られる場所で、生体分子は自然に合成されたと考えている。

アイディアと最先端技術で解き明かす

そこでまずチャンドゥルーは、生体分子ができたであろう”原始の地球の環境”を実験室内に再現しようというのだ。生体分子は高温では不安定であることから、生体分子ができた原始の地球は低温であったされている。ただ、局地的にさまざまな環境が存在しており、その中に生体分子ができやすい環境があったと考えられる。
１つは、ユーリー・ミラーの実験のように、落雷によって一瞬だけ高温になり、その後急激に冷えるという条件をフラスコ内につくる。これは浅い海の環境を再現するもので、「低温地球シミュレータ」と呼んでいる。設計図は完成し、現在、製作作業が進んでいる。実験では、一酸化炭素や二酸化炭素、アンモニア、メタン、水素など、フラスコ内のガスの組成によって、生体分子であるアミノ酸や脂質のでき方がどう変わるかを検討する予定だ。
一方、生体分子ができたとされるもう1つの候補地、海底の熱水噴出孔周辺で何が起こったのかは、「フロー式急冷リアクタ」で検討する（図2）。この装置の特徴は、熱水孔内部は高温でありながら、その周辺は海水の影響で一気に冷えるという環境を再現できることだ。しかも、そこには流れがあり、一瞬として環境が安定することがない。こうした環境下において、一酸化炭素や二酸化炭素といった単純な分子から、生体分子の元ともいえる炭化水素類の合成を試みる。
「2つの装置内の温度、pH、気体や溶液の組成などを変えることで、考えられる限りの原始の地球の環境を再現し、そこでどんな生体分子ができるか検討します」とチャンドゥルー。「この実験では、最終的な生体分子が何であるかだけでなく、それができる過程でどのような物質ができたり無くなったりしているのか、途中の段階も１つ１つ突き止めたいのです」。質量分析装置など、少量の物質の同定を可能にしてくれる最新分析機器もそろった。間もなく装置も完成の予定（2015年7月時点）で、ひたすら実験を繰り返す日々が始まる。

図2.jpg
図2：海底の熱水噴出孔の環境を再現する「フロー式急冷リアクタ」。流れ（フロー）の中で、生体分子の合成反応が進む点が、これまでの多くの学者たちが行ってきた実験と異なる。

期待の大きさ

kuhan02.jpg「生体分子が生成すれば、生命が成り立つわけではありません。生体分子の１つである脂質は、細胞膜など構造にならなくてはなりませんし、その中で代謝といったエネルギー変換が行われ、自己複製ができるようになって初めて生命だからです。細胞膜や代謝にももちろん興味はあります。しかし、生体分子ができなければ生命は誕生しない。私がやろうとしているのは、生命誕生のごく最初に起こった出来事の解明なのです」。チャンドゥルーの実験計画は、生命誕生の謎に迫るものだとして、平成27年度の笹川科学研究助成を受けることになった。
ELSIの外国人研究者では、初めて日本の助成金を獲得した。
生命誕生から38億年。その最初に起こった生体分子生成の現場を目の当たりにする日は、すぐそこまできているのかもしれない。

人物紹介

006.jpgマレーシア出身のチャンドゥルー。趣味はサッカー。ポジションはミッドフィールダー。2010年に来日以来、東京や横浜を中心に仲間を募り、サッカーチームを結成し活動している。今回、計画中の実験については、「装置をつくったり、実験を進めたりする優秀なメンバーは揃いました。あとは、化学に精通したアドバイザーがいてくれるといいのですが」。ELSIのバックアップを受け、チャンドゥルーの結成した研究チームのチャレンジが始まる。

 

 

Original interview appeared on February 2015 ELSI (Japanese) 

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

Posted on by Kuhan Chandru
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

Posted on by Kuhan Chandru

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!

From Russia with love: another meteorite explosion

Posted on by Kuhan Chandru

A meteorite like object lit up the skies at the wee hours at Murmansk, Russia (check the video footage out). There is a possibility that the object is part of the Lyrid meteor shower which happens annually when it’s nearing its peak. I find this amazing as this is the second time this is happening in Russia (northern hamisphere??). In February 2013, a surprise asteroid about 20 metres and 5,000 kilograms came across the sky over Chelyabinsk, Russia. The blast from its explosion was worth millions of euros worth of damages and injured over 1,000 people. Nobody saw it coming. I am aware that almost every day the Earth gets hit with hundreds of tons of material from space, most of them ranges from the size of a grain of sand to something of an object the size of a sim card. This kind of meteorite strikes (for the second time) kinda scares me a little, its like a sign that every now and then a meteorite or asteroid can hit us and exterminate life as we know it. Gosh, I am thinking about the extincted dinosaurs now, or worst, aliens rising from them.

Submarine Hydrothermal system (SHS) and the link to origin of life

Posted on by Kuhan Chandru

http://www.whoi.edu/cms/images/lstokey/2005/1/v41n2-tivey1en_5063.jpg

Plate tectonic is the theory which unified on how the earth worked. The theory has always been there (since 1879)1,2 and was only accepted in the 1950‘s. The theory also predicted the existence of hydrothermal vents; a deep-sea hot springs is formed when cold seawater seeps into magma-emitting cracks on the oceanic surface, heats up, and rises. Although scientists had been actively searching for vents since the early 1960s, it wasn’t until the 1977; when the Galápagos Hydrothermal Expedition led by Richard Von Herzen and Robert Ballard of the Woods Hole Oceanographic Institution, that confirmed their existence using the famous submersible, Alvin ,3,4.

The relationship between SHS and origin of life on the other hand, first came out through Jack Corliss, John Baross and Sarah Hoffman5. They claimed that the conditions surrounding the vent area provided all the conditions for life’s creation on earth. Over time this idea has sprouted and have been elaborated with many in-situ integration with simulation data. I will elaborate more on this in the next post.

  1. Darwin, G.H (1879) On the procession of viscous spheroid, and on the remote History of the Earth.Philosophical Transactions of the Royal Society of London Vol. 170, 447-538
  2. McKenzie, D. P (1969) Speculations on the consequences and causes of plate motions. Geophysical Journal International, 18(1), 1–32.
  3. Corliss, J. B. J, Baross, J.A and Hoffman, S.E (1981) An hypothesis concerning the relationship between submarine hot springs and the origin of life on Earth.  Oceanologica Acta 4, 59-69.
  4. Corliss, J.B, Lyle, M, Dymond. J and Crane, K (1978) The chemistry of hydrothermal mounds near the Galapagos Rift. Earth and Planetary Science Letters, Volume 40, Issue 1,12–24.
  5. Corliss, J.B, Baross, J.A. and Hoffman, S.E (1981) An hypothesis concerning the relationship between submarine hot springs and the origin of life on Earth, Oceanologica Acta 4, 59–69

Cellrelics wishes you a Happy New Year

Posted on by Kuhan Chandru

Happy new year. I hope 2012 wil be an eventful and fruitful year to all my readers. Thank you for following my humble writings. Below is a 2011 review of the blog

The WordPress.com stats helper monkeys prepared a 2011 annual report for this blog.

Here’s an excerpt:

A San Francisco cable car holds 60 people. This blog was viewed about 1,600 times in 2011. If it were a cable car, it would take about 27 trips to carry that many people.

Click here to see the complete report.