Opinion

It’s time to exploit your favorite quirkyorganism with new technologies
Haruhiko SiomiWe live in a competitive world
where, at any given moment, ourpeers might achieve the very
discoveries we hope to make with our own
research. This reality creates butterflies inthe stomachs of those who are engaged inrisky experiments. Any hesitation or setback,even momentary, can make you feel that by
the time you are in a position to pursue yourown direction, every novelty will alreadyhave been discovered. But don’t worry, formany years to come there will be plenty ofbiology waiting to be investigated with manyquestions we haven’t yet thought of asking.
I think that the most important field inbiology today is developmental biology.
During development, it is thought that each
event or structure is consequential to apreceding event or structure and that thelayering of subsequent processes ultimately
brings the phenotype into being. This
process is also studied by those in the field
we now call epigenetics, which, I believe, ismodern developmental biology armed withstate-of-the art genomics tools and systems
bioinformatics. I want to know how a fertilized egg with one genome can give rise to adazzling variety of cell types in which all
genomes are the same as that of the egg, andhow these cells are organized to form a functional whole at the end of ontogeny. I verymuch want to decode where and how in thegenome or cell the storage and retrieval ofthe ‘memory’ of ordered sequences of events
that contribute to the elaboration of complex
developmental patterns is achieved. I havelearned that if we ask the right questions, wecan learn fundamental truths about how andwhy life is the way it is. Unfortunately,
however, I don’t know the right questions
that can be refined and tested experimentallyby the broader scientific community that will

unlock the mysteries of development. I am,
nevertheless, optimistic.
In the past three decades, we have discovered the striking wholesale conservation ofmolecular mechanisms across the world of
eukaryotes. My favorite paper is by Halder,
Callaerts, and Gehring, published in 1995, in
which they show that ectopic expression ofmouse Pax6 cDNA under the control ofGAL4 induces the formation of ectopic eyes
on a fly leg [1]. We have also learned thatwhat is learned in one species will lead to
new approaches and principles that can betransferred to more complicated cells andanimals. I particularly like the RNAi paper
by Tuschl and colleagues, published in 2001,
which demonstrates that 21-nucleotide
siRNA duplexes specifically suppress expression of endogenous and heterologous genes
in different mammalian cell lines [2]. The
realization that the number of genes does
not increase proportionally with developmental complexity has led to the conclusionthat regulation of gene expression is more
important than simply the number of genes
in a genome. We are also well aware thatspecial elaborations and exaggerations ofcertain basic eukaryotic mechanisms in
unusual organisms have often facilitateddiscoveries opening the door to major new
fields of fundamental research. Elizabeth
Blackburn thoughtfully used Tetrahymena tostudy the function of telomeres and, thereby,
identified telomerase [3]. David Allis also
used Tetrahymena to study histone modifications. This eventually led to the first identification of a nuclear histone acetyltransferase(HAT) as the homolog of the yeast transcriptional factor, GCN5, and, thereby, the realization that transcriptional regulators can act
by modifying chromatin [4]. Tetrahymena isa single-celled organism and exhibits nuclear

dimorphism; each cell has two nuclei, themicronucleus, which contains the germline
genome and is transcriptionally silent, andthe macronucleus containing the somaticgenome, which becomes transcriptionallyactive, hyperacetylated, and highly fragmented—that is, many chromosomes requiring telomeres. These scientists clearly had
the open minds needed to ask the right questions of the right model organism.
We live in an era where advances in DNA
sequencing technology allow an individual
scientist to determine the whole-genome
sequence and the entire transcriptome ofany organism in a matter of days. Methods
for manipulating gene expression—RNAi,TALENs, and CRISPR/Cas9, for example—
are also increasingly employed. With these
new technologies, the constraints of relying
solely on traditional model organisms arereleased. Rather, any favorite animal orplant that is best studied to resolve the problems under scrutiny can be adopted as amodel organism. Thus, the suitability of amodel organism has to be redefined in termsof how developed and elaborated is the basic
eukaryotic feature that you want to resolve.
Progress in biology is driven by new scientific questions, which demand not only newtechnology, but often new model organisms.
The beginning of the molecular biology era—the 1950s and 1960s—was stimulated bymany physicists who moved into the field;
hence, we perhaps now need people whobring with them a happy ignorance of classical model organisms.
How can we identify new model organisms? Just like development, science
progresses not by creating anything whollyde novo by chance, but by integrating thepreceding knowledge with the new. As theold Chinese proverb goes: “he that would

Department of Molecular Biology, Keio University School of Medicine, Shinjuku-ku, Japan. E-mail: awa403@z2.keio.jp
DOI 10.15252/embr.201438955ª 2014 The Author

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know what shall be must consider what hasbeen”. A conservative approach, therefore,
is to go to the library and search through oldjournals. I used to love walking throughsilent alleys of book shelves to occasionallyfind very strange but interesting papers,such as ‘Planarians and memory’, which
describes the transfer of learning by theinjection of ribonucleic acid (now, that, I
think, is cool!) [5]. Alternatively, an exploration of the plethora of wild species may yetyield your favorite quirky organism.
By the way, if you are wondering whether
I have a favorite odd organism, the answer is2

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Opinionyes: it’s the naked mole rat [6]. They look
really quirky and cute, and they can live formore than thirty years without any sign ofcancer. But they are already popular, so I
should go out to the library or out into thewild to hunt for new peculiar organisms. Oh,I nearly forgot that I should identify the problems I want to solve before I leap. For me:
the organic memory of ordered sequences ofevents.

Conflict of interest
The author declares that he has no conflict ofReferences1.

Halder G, Callaerts P, Gehring WJ (1995)
Science 267: 1788 – 1792

2.

Elbashir SM, Harborth J, Lendeckel W et al3.

Blackburn EH, Greider CW, Szostak JW (2006)(2001) Nature 411: 494 – 498
Nat Med 12: 1133 – 1138
4.

Brownell JE, Zhou J, Ranalli T et al (1996) Cell84: 843 – 851

5.

Jacobson AL, Fried C, Horowitz SD (1966)
Nature 209: 599 – 601

6.

Sedivy JM (2009) Proc Natl Acad Sci USA 106:19207 – 19208

interest.

ª 2014 The Author