PreprintPDF Available

Minimal embryos and minimal cancers

Authors:
  • Oxford Advanced Research Foundation
Preprints and early-stage research may not have been peer reviewed yet.

Abstract and Figures

Craig Venter’s group has set yet another scientific milestone by creating the second synthetic cell (Syn 3.0). Like the first synthetic cell its genome was constructed on the computer, and then inserted into a cell, jump-started and made to grow and divide. The significance of a few artificial cells with designed genomes growing in a dish cannot be overestimated. The next step is to create minimal multicellular systems. That will allow us to study embryogenesis and development in detail. One can then also create and study minimal cancers allowing us to study cancer in an unprecedented way.
Content may be subject to copyright.
Minimal'embryos'and'minimal'cancers1'
Eric'Werner,'University'of'Oxford2''
!
"#$%&!'()*(#+,!&#-./!0$,!,(*!1(*!$)-*0(#!,2%()*%3%2!4%5(,*-)(!61!2#($*%)&!*0(!,(2-)7!,1)*0(*%2!2(55!
891)!:;<=;!>%?(!*0(!3%#,*!,1)*0(*%2!2(55!%*,!&()-4(!@$,!2-),*#.2*(7!-)!*0(!2-4/.*(#A!$)7!*0()!
%),(#*(7!%)*-!$!2(55A!B.4/C,*$#*(7!$)7!4$7(!*-!&#-@!$)7!7%D%7(;!E0(!,%&)%3%2$)2(!-3!$!3(@!$#*%3%2%$5!
2(55,!@%*0!7(,%&)(7!&()-4(,!&#-@%)&!%)!$!7%,0!2$))-*!6(!-D(#(,*%4$*(7;!>(*!4(!*(55!1-.!@01F!
G)!H<<I!G!@$,!%)D%*(7!*-!&%D(!$!*$5?!$*!$!,14/-,%.4!%)!0-)-#!-3!*0(!J-6(5!5$.#($*(!K$#!L-6%)7!
M0-#$)$;!G*!2-),%,*(7!4-,*51!-3!J-6(5!5$.#($*(,!%)25.7%)&!N$#,0$55!J%#()6(#&!8@0-!6#-?(!*0(!
&()(*%2!2-7(!@%*0!M0-#$)$=;!O5,-!$4-)&!*0(!J-6(5!P#%Q(!@%))(#,!@$,!K$4%5*-)!94%*0!-)(!-3!
'()*(#+,!5($7!,2%()*%,*,;!94%*0!$)7!K$#D$#7!/#-3(,,-#!L(-#&(!"0.#20!7(,2#%6(7!*0(%#!&-$5!-3!
2#($*%)&!$)!$#*%3%2%$5!2(55!2-)*#-55(7!61!$!&()-4(!*0$*!*0(1!7(,%&)(7!-)!*0(!2-4/.*(#;!
!
Figure'1'George'Church'(Harvard),'Eric'Werner'(Oxford),'Marshall'Nirenberg'(Nobel'Laureate)'
!
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
R!S,,$1!,.64%**(7!*-!J(@!T-#?!E%4(,!HU!N$#20!H<RU;!"-/1#%&0*!S#%2!V(#)(#!H<RU;!O55!#%&0*,!
#(,(#D(7;!!P$#*!-3!41!,(#%(,!WO#(!1-.!,4$#*(#!*0$)!*0(!$D(#$&(!J(@!T-#?!E%4(,!#($7(#XY!9((F!!
0**/,FZZ(#%2@(#)(#;2-4!!
!
H!P#(,()*!$,,-2%$*%-)F![\3-#7!O7D$)2(7!](,($#20!^-.)7$*%-)A!0**/,FZZ-$#3;-#&!!
S4$%5F!(#%2;@(#)(#_-$#3;-#&!!
N1!*$5?!@$,!$6-.*!@0$*!0$//(),!%3!'()*(#+,!&#-./!@$,!,.22(,,3.5;!!O!1($#!5$*(#!'()*(#!$))-.)2(7!
*0(%#!,.22(,,;!G)!N$#20!*0%,!1($#!*0(1!$))-.)2(7!*0(%#!,(2-)7!$#*%3%2%$5!2(55!*0$*!#.),!-)!$!)(@51!
7(,%&)(7!(D()!,4$55(#!&()-4(;!!
So'what'can'happen'next?''
'()*(#+,!/#-&#$4!%,!#(,*#%2*(7!*-!6$2*(#%$A!,%)&5(!2(55(7!-#&$)%,4,;!V(!0-@(D(#!$#(A!-3!2-.#,(A!
4.5*%C2(55.5$#!-#&$)%,4,;!!!^-#!1($#,!41!*($4!$)7!G!0$D(!6(()!7(,%&)%)&!*0(!&()-4(,!-3!4.5*%C
2(55.5$#!-#&$)%,4,!-)!*0(!2-4/.*(#!$)7!*0()!4-7(5%)&!$)7!,%4.5$*%)&!*0(!7(D(5-/4()*!-3!4.5*%C
2(55.5$#!-#&$)%,4,!%)!`C7%4(),%-)$5!,/$2(C*%4(;!T-.!2$)!,((!*0(!-#&$)%,4!&#-@!-)!*0(!2-4/.*(#;!
G3!1-.!20$)&(!*0(%#!&()-4(!1-.!,((!*0(!20$)&(!%)!*0(!2-4/.*(#C&()(#$*(7!-#&$)%,4;!!
!
Figure'2'A'simulation'of'a'fast'growing'tumor'
!
E0%,!%,!@01!*0(!@-#?!-3!'()*(#+,!&#-./!,-!%4/-#*$)*;!G*!-/(),!$!/$*0!*-!2#($*%)&!$#*%3%2%$5!4.5*%C
2(55.5$#!,1,*(4,A!5%?(!*%,,.(A!-#&$),A!4%)%4$5!(46#1-,A!$)7!4%)%4$5!4.5*%C2(55.5$#!-#&$)%,4,;!a1!$!
4%)%4$5!4.5*%C2(55.5$#!-#&$)%,4!G!4($)!-)(!@0-,(!,/$#,(!&()-4(!%,!7(,%&)(7!-)!*0(!2-4/.*(#A!
*0()!*#$),5$*(7!%)!)$*.#$5!bJO;!E0(!bJO!%,!3-#4(7!%)*-!-)(!-#!4-#(!20#-4-,-4(,!$)7!*0()!
%),(#*(7!%)*-!$)!(&&!@0-,(!-@)!&()-4(!%,!#(/5$2(7!61!*0(!)(@!,1)*0(*%2!&()-4(;!^%)$551A!*0(!)(@!
,1)*0(*%2!(&&!%,!B.4/!,*$#*(7A!c6--*(7C./+A!*-!&#-@!%)*-!$!,*#.2*.#(!-3!2(55,!-#!$!2-4/5(*(!-#&$)%,4!
4.20!5%?(!*0(!-)(!7(,%&)(7!$)7!4-7(5(7!-)!*0(!2-4/.*(#;!!
E0%,!4(*0-7-5-&1!%,!,%4%5$#!*-!*0(!@$1!@(!7(,%&)!*(,*!2$#,!$)7!$%#/5$)(,!@%*0!"Ob!8"-4/.*(#!
O%7(7!b(,%&)=!/#-&#$4,!/#%-#!*-!$2*.$551!6.%57%)&!*0(4;!E0(!@0-5(!/#-2(,,!-3!7(,%&)%)&!4.5*%C
2(55.5$#!-#&$)%,4,!@$,!7(,2#%6(7!$)7!/.65%,0(7!%)!,2%()*%3%2!B-.#)$5,!1($#,!6(3-#(!'()*(#+,!&#-./!
,*$#*(7!*0(%#!/#-B(2*!@%*0!,%)&5(!2(55(7!-#&$)%,4,;![)51!)-@!-.#!/#-B(2*!%,!4.20!25-,(#!*-!6(%)&!
#($5%Q(7;!!!
P$#$7%&4!,0%3*%)&!*(20)-5-&1!5%?(!,2%()2(!/#-2((7,!%)!B.4/,!,.#/#%,%)&!.,!@%*0!%*,!#$/%7%*1;!E0(#(!
4$1!6(!1($#,!-#!2()*.#%(,!6(*@(()!*0(!4$B-#!B.4/,!6.*!@0()!%*!0$//(),!%*!20$)&(,!(D(#1*0%)&!@(!
$#(!3$4%5%$#!@%*0;!9-!%*!%,!@%*0!'()*(#+,!@-#?;!V0()!2-46%)(7!@%*0!-.#!@-#?!%*!5($7,!*-!$)!
$,*-.)7%)&A!(D()!%3!)-*!,0-2?%)&!3.*.#(;!!
92%()2(!3%2*%-)!%,!,-4(*%4(,!$0($7!-3!,2%()2(;!9-!6(2$.,(!-3!K-551@--7!3%54,!)-*0%)&!4$1!,0-2?!
.,;!E0(%#!$)%4$*%-),!4$1!4$?(!$)1*0%)&!,((4!#($5;!G)!3$2*!*0(!4.20!-3!K-551@--7!$)%4$*%-),!$#(!
&()(#$*(7!.,%)&!/#-&#$4,!*0$*!4-7(5!*0(!4$*0(4$*%2,!-3!#($5!/01,%2,!*-!,%4.5$*(!*0(!6-.)2%)&!-3!
20$#$2*(#,!$)7!6#($?%)&!-3!6.%57%)&,A!(*2;!a.*!-3!2-.#,(!*0(1!6#($?!#($5!5$@,!*-!&$%)!,./(#4$)C5%?(!
(33(2*,;!!!
"-4/.*(#!4-7(5%)&!$)7!,%4.5$*%-),!.,(7!%)!"Ob!/#-&#$4,!$#(!)-*!B.,*!$)%4$*%-),;!E0(1!2$/*.#(!
$)!$,/(2*!-3!#($5%*1;!E0(1!2$)!6(!.,(7!*-!/#(7%2*!*0(!6(0$D%-#!-3!#($5!,1,*(4,;!9-!%*!%,!@%*0!"Ob!
/#-&#$4,!*0$*!4-7(5!4.5*%C2(55.5$#!7(D(5-/4()*!-3!(46#1-)%2!&#-@*0;!V(!2$)!5($#)!$!&#($*!7($5!
$6-.*!#($5!(46#1-,!61!,%4.5$*%)&!*0(!/#-2(,,(,!*0$*!2-)*#-5!*0(%#!7(D(5-/4()*;!!!
[)(!-3!*0(!6%&!/#-65(4,!*0$*!G!0$D(!@-#?(7!-)!%,!0-@!2$)2(#!@-#?,;!V(!2$)!7(,%&)!$)7!,%4.5$*(!
4$)1!*1/(,!-3!2$)2(#+,!71)$4%2,!-)!*0(!2-4/.*(#;!G)!3$2*!G!c7%,2-D(#(7+!2$)2(#!-)!*0(!2-4/.*(#d!
V0()!,%4.5$*%)&!*0(!7(D(5-/4()*!-3!,%4/5(!(46#1-,A!,-4(!6(&$)!*-!&#-@!.)2-)*#-55$651!4.20!
5%?(!#($5!2$)2(#,;!O*!3%#,*!/.QQ5(7A!G!e.%2?51!2$4(!*-!.)7(#,*$)7!0-@!,.20!2-4/.*(#C&()(#$*(7!
2$)2(#,!@-#?!$)7!0-@!*0(1!2$)!6(!,*-//(7;!!
E0%,!5(7!4(!*-!*0(!3$,2%)$*%)&!e.(,*%-)F!K-@!$#(!*0(,(!2-4/.*(#C&()(#$*(7!2$)2(#,!$#(!#(5$*(7!*-!
5%D(!2$)2(#,;!9-!6(&$)!$!5-)&!#-$7!*-!.)7(#,*$)7%)&!0-@!#($5!2$)2(#,!$#(!2-)*#-55(7!$)7!0-@!*0(1!
2$)A!%)!/#%)2%/5(A!6(!,*-//(7;!V(!2$)!,*-/!2$)2(#,!-)!*0(!2-4/.*(#;!O)7A!-)2(!@(!$#(!$65(!*-!
&()(#$*(!,1)*0(*%2!4.5*%C2(55.5$#!-#&$)%,4,!@(!@%55!$5,-!6(!$65(!*-!&#-@!,1)*0(*%2!2$)2(#,;!O)7!@(!
@%55!&$%)!*0(!*--5,!*-!,*-/!,1)*0(*%2!2$)2(#,;!E0%,!2$)!5($7!*-!*(20)-5-&%(,!*-!2.#(!)$*.#$5!2$)2(#,!
%)!#($5!0.4$),;!!!
V0%5(!*0(#(!%,!4.20!#(,($#20!6(3-#(!*0%,!@%55!6(2-4(!#($5%*1A!2-4/.*(#!,%4.5$*%-),!-3!2$)2(#,!$)7!
-*0(#!4.5*%C2(55.5$#!7%,($,(,!2$)!0(5/!.,!.)7(#,*$)7!*0(%#!(,,()2(;!E0%,!-/(),!*0(!7--#!*-!)(@!
#(,($#20A!4(7%2$5!/#$2*%2(!$)7!*0(#$/%(,!(D()!@0%5(!@(!$)*%2%/$*(!*0(!7(D(5-/4()*!-3!,1)*0(*%2!
2$)2(#!#(,($#20;!!!!!
E0.,A!$,!G!$#&.(7!%)!,2%()*%3%2!B-.#)$5,!@(!2-.57!%)!/#%)2%/5(!#(D(#,(!()&%)((#!$!&()-4(!*#$),5$*%)&!
%*!%)*-!$)!$#*%3%2%$5!&()-4(!*0$*!@0()!%),(#*(7!%)*-!D%#*.$5!2(55!2-.57!&()(#$*(!$!2-##(,/-)7%)&!
D%#*.$5!4.5*%C2(55.5$#!,1,*(4;!!L-%)&!%)!*0(!-*0(#!7%#(2*%-)A!%)!/#%)2%/5(!@(!2-.57!7(,%&)!$)!$#*%3%2%$5!
D%#*.$5!&()-4(!*0$*!&()(#$*(,!$!D%#*.$5!4.5*%C2(55.5$#!,1,*(4A!8*%,,.(A!-#&$)!-#!-#&$)%,4=!-)!*0(!
2-4/.*(#;!!J(\*A!@(!*#$),5$*(!*0(!7(,%&)(7!&()-4(!%)*-!%*,!)$*.#$5!bJO!()2-7%)&;!E0()!@(!
,1)*0(,%Q(!*0(!$2*.$5!20#-4-,-4(,;!!E0(,(!7(,%&)(7!$)7!,1)*0(,%Q(7!20#-4-,-4(,!$#(!*0()!
%),(#*(7!%)*-!$!2(55;!V0()!6--*(7C./A!*0%,!2(55!*0()!&()(#$*(,!$)!(e.%D$5()*A!6.*!5%D%)&A!7(,%&)(7A!
4.5*%C2(55.5$#!,1,*(4;!!!
E0(!)$*.#(!-3!*0(!D%#*.$5!$)7!)$*.#$5!-#&$)%,4,!$)7!*0(%#!&()-4(,!%,!D(#1!7%33(#()*!1(*!*0(!7#%D%)&!
2-)*#-5!%)3-#4$*%-)!%)!*0(%#!7(D(5-/4()*$5!)(*@-#?,!%,!3.)2*%-)$551!*0(!,$4(!%)!6-*0;!!!
'()*(#+,!&#-./!0$,!$5#($71!7-)(!*0%,!3-#!,%)&5(C2(55(7!-#&$)%,4,;!G)!*0$*!*$5?!G!&$D(!$*!*0(!,$4(!
,14/-,%.4!@0(#(!'()*(#+,!&#-./!/#(,()*(7!*0(%#!/5$),!*-!2#($*(!,.20!$!2(55A!G!-.*5%)(7!0-@!*-!
7(,%&)!$!D%#*.$5!&()-4(!$)7!$!D%#*.$5!4.5*%C2(55.5$#!-#&$)%,4!$)7!*0()!*#$),5$*(!*0$*!$#*%3%2%$5!
&()-4(!%)*-!%*,!)$*.#$5!&()-4(A!%),(#*!*0$*!&()-4(!%)*-!$)!(&&!$)7!*0()!&#-@!*0(!7(,%&)(7!#($5!
4.5*%C2(55.5$#!-#&$)%,4;!!!
G*!*$?(,!$!D%#*.$5!4-7(5!$)7!2#($*(,!$!#($5!4-7(5!-#&$)%,4;!G3!*0(!#(,.5*%)&!#($5!-#&$)%,4!%,!
7%33(#()*!*0$)!*0(!D%#*.$5!7(,%&)(7!-#&$)%,4!*0()!@(!20$)&(!-.#!D%#*.$5!-#&$)%,4!C!(%*0(#!%*,!
&()-4(!-#!*0(!/#-/(#*%(,!-3!%*,!D%#*.$5!(&&!C!$)7!#(7-!*0(!*#$),5$*%-)!$)7!&#-@*0!-3!*0(!#($5!
-#&$)%,4;!!O)7A!,-!-);!O5*(#)$*%D(51A!@(!20$)&(!*0(!#($5!(&&!$)7!%*,!/#-/(#*%(,;!E0#-.&0!*0%,!
3((76$2?!5--/!@(!&#$7.$551!3%*!*0(!D%#*.$5!&()-4(!$)7!(&&!@%*0!*0(!#($5!&()-4(!$)7!(&&;!!
b.(!*-!3$%5.#(,!%)!*0(%#!$**(4/*!*-!7(,%&)!2(55!&()-4(,!.,%)&!(\/(#*!?)-@5(7&(!'()*(#!(\/#(,,(7!
,?(/*%2%,4F!c-.#!2.##()*!?)-@5(7&(!-3!6%-5-&1!%,!)-*!,.33%2%()*!*-!,%*!7-@)!$)7!7(,%&)!$!5%D%)&!
-#&$)%,4!$)7!6.%57!%*;+!!
K-@(D(#A!'()*(#+,!@-#?!%,!@%*0!6$2*(#%$!$)7!%,!&#-.)7(7!%)!$!&()(C2()*#%2!4-7(5!-3!5%3(;!O,!G!
$#&.(7!(5,(@0(#(A!-)51!5(,,!*0$)!fg!-3!-.#!&()-4(!2-),%,*,!-3!&()(,;!V0%5(!&()(,!4$1!2-)*#-5!
6$2*(#%$A!4.5*%C2(55.5$#!5%3(!%,!2-)*#-55(7!61!)(*@-#?,!%)!*0(!)-)C&()(*%2!$#($!-3!*0(!&()-4(!*0$*!
4$?(,!./!*0(!-*0(#!Ifg;!!G*!4$1!@(55!*.#)!-.*!*0$*!@(!.)7(#,*$)7!*0(!2-7(!-3!)(*@-#?,!*0$*!
2-)*#-5!*0(!7(D(5-/4()*!-3!(46#1-,!6(3-#(!@(!.)7(#,*$)7!*0(!3.)2*%-)%)&!-3!*0-,(!H<A<<<!-#!,-!
&()(,;!!
G!5($D(!1-.!@%*0!$!@-#7!$6-.*!h.#$,,%2!P$#?F!V(!0$D(!6(()!7(6$*%)&!*0(,(!%,,.(,!3-#!1($#,!%)!
,(4%)$#,!G!0(57!$*!*0(!i)%D(#,%*1!-3![\3-#7+,!-57(,*!2-55(&(!a$55%-5!8$5*0-.&0!(D()!%*,!$&(!%,!
7(6$*(7d=!G)!$)!(,,$1!G!/#(,()*(7!*-!*0(!,(4%)$#A!G!,*$*(7!0-@!@(!2$)!7(,%&)A!2#($*(!$)7!/#(C
/#-&#$4!$!/#(/$#$*-#1!&()-4(!*0$*!%)%*%$*(,!$!.)%D(#,$5!(&&!*-!/#(/$#(!%*!2--/(#$*(!@%*0!*0(!
&()-4(!-3!$!)$*.#$5!-#&$)%,4;!G)!*0%,!@$1A!@(!2-.57!7(,%&)!$)!(&&!*-!6(!2-4/$*%65(!@%*0!*0(!
&()-4(!-3!$)!-#&$)%,4!,-!*0$*!@(!2$)!25-)(!*0$*!-#&$)%,4!(D()!%3!@(!7-)+*!0$D(!*0(!-#%&%)$5!(&&A!
$,!%,!*0(!2$,(!@%*0!(\*%)2*!,/(2%(,;!!
O55!*0%,!%,!$!5-*!*-!/#-2(,,A!6.*!%*!%,!%4/-#*$)*!*-!#($5%Q(!@0$*!$@$%*,!.,;![*0(#@%,(!*0(!3.*.#(!@%55!
#.)!-D(#!.,d!V(!@%55!6(!$65(!*-!2#($*(!2$)2(#,!6.*!@(!@%55!$5,-!6(!$65(!*-!2.#(!*0(4;!!
!
>%)?,F!!
http://science.sciencemag.org/content/351/6280/aad6253!
http://users.ox.ac.uk/~dpag0022/!!
a5-&F!!http://cancerclearworld.wordpress.com!
V(#)(#A!SA!c"$)2(#!J(*@-#?,F!O!&()(#$5!*0(-#(*%2$5!$)7!2-4/.*$*%-)$5!3#$4(@-#?!3-#!
.)7(#,*$)7%)&!2$)2(#+A!$#j%DFRRR<;fkUfDR!leC6%-;!NJmA![2*!HUA!H<RR;!
>%)?F!http://arxiv.org/abs/1110.5865!
V(#)(#A!S;A!WE0(!^.*.#(!$)7!>%4%*,!-3!91,*(4,!a%-5-&1YA!92%()2(!9EMS!H<<fA!/(RU!8H<<f=;!
V(#)(#A!S;A!WL()-4(!9(4$)*%2,A!G)!9%5%2-!N.5*%2(55.5$#!91,*(4,!$)7!*0(!"()*#$5!b-&4$YA!^Sa9!
>(**(#,!fnIA!//!RnnICRnkH!8N$#20!HRA!H<<f=!
V(#)(#A!S;A!WG)!,%5%2-!4.5*%2(55.5$#!,1,*(4,!6%-5-&1!$)7!4%)%4$5!&()-4(,YA!bbE!b#.&!b%,2-D(#1!
E-7$1A!D-5!kA!)-!H`A!//!RRHRCRRHnA!b(2!H<<:;!!
Preprint
Full-text available
All diploid sexual organisms have two distinct haploid genomes, one from each parent. There is the male derived haploid genome and the female derived haploid genome. Each genome contains a distinct developmental control network that directs the development of the embryo to an adult. Run separately, independent of the influence of the other network, the each haploid genome produces a morphologically different organism. The interrelationship of the male and female haploid genome networks is governed by an interaction protocol that determines which parental network is in control in any given cell at any given point in development. The protocol consists of two interacting half-protocols, one for each parental hap-loid genome. The full interaction protocol is itself a higher-level, meta-network, or internetwork between the two lower-level, parental developmental control networks. Computer simulations show that if the interaction protocol is random then there is a loss of bilateral symmetry in the generated organism. Therefore, for all bilaterally symmetric organisms, the interaction protocol between the two parental genomes cannot be random. This implies that a nonrandom ur-protocol must have evolved with the first diploid bilaterians in the Precambrian more than 570 million years ago. Nonrandom protocols partition the embryo and adult into dynamic sections that are variably controlled by one or the other parental haploid genome network. Developmental networks and their meta-network protocols provide fundamentally new insights into embryonic and post-embryonic development, developmental pathologies, animal and plant hybrids, heterosis, and evolutionary dynamics.
Article
Full-text available
We present a general computational theory of cancer and its developmental dynamics. The theory is based on a theory of the architecture and function of developmental control networks which guide the formation of multicellular organisms. Cancer networks are special cases of developmental control networks. Cancer results from transformations of normal developmental networks. Our theory generates a natural classification of all possible cancers based on their network architecture. Each cancer network has a unique topology and semantics and developmental dynamics that result in distinct clinical tumor phenotypes. We apply this new theory with a series of proof of concept cases for all the basic cancer types. These cases have been computationally modeled, their behavior simulated and mathematically described using a multicellular systems biology approach. There are fascinating correspondences between the dynamic developmental phenotype of computationally modeled {\em in silico} cancers and natural {\em in vivo} cancers. The theory lays the foundation for a new research paradigm for understanding and investigating cancer. The theory of cancer networks implies that new diagnostic methods and new treatments to cure cancer will become possible.
Article
Full-text available
The in vivo and in silico understanding of genomes and networks in cellular and multicellular systems is essential for drug discovery for multicellular diseases. In silico methodologies, when integrated with in vivo engineering methods, lay the groundwork for understanding multicellular organisms and their genomes. The quest to construct a minimal cell can be followed by designed, minimal multicellular organisms. In silico multicellular systems biology will be essential in the design and construction of minimal genomes for minimal multicellular organisms. Advanced methodologies come to light that can aid drug discovery. These novel approaches include multicellular pharmacodynamics and networked multicellular pharmacodynamics.
Article
Full-text available
Genomes with their complexity and size present what appears to be an impossible challenge. Scientists speak in terms of decades or even centuries before we will understand how genomes and their hosts the cell and the city of cells that make up the multicellular context function. We believe that there will be surprisingly quick progress made in our understanding of genomes. The key is to stop taking the Central Dogma as the only direction in which genome research can scale the semantics of genomes. Instead a top-down approach coupled with a bottom-up approach may snare the unwieldy beast and make sense of genomes. The method we propose is to take in silico biology seriously. By developing in silico models of genomes cells and multicellular systems, we position ourselves to develop a theory of meaning for artificial genomes. Then using that develop a natural semantics of genomes.
Article
Systems biology has enjoyed explosive growth in both the number of people participating in this area of research and the number of publications on the topic. And yet, the paradigms that underlie the field have not seen a similar expansiveness. Instead, most of these paradigms have been carried over from other fields like engineering, physics, and mathematics. As a result, a small set of concepts dominate the field. The traditional biologist is seen by many as outmoded and tolerated only as a source of data. In this view, the biologist's ideas may even be considered conceptually and theoretically irrelevant. In this Perspective, we take a critical look at some of the paradigms of systems biology and question whether the biologist's ideas, methods, and theories have really become outmoded. We see the future of systems biology as a tight coupling of in vivo and in vitro methods for bioengineering with in silico multicellular modeling and simulation.