biological systems also physical systems? Shant Shahbazian Faculty - - PowerPoint PPT Presentation

The age of the “synthetic” biology: Are biological systems also physical systems?

Shant Shahbazian Faculty of physics, Department of complex and biological systems, Shahid Beheshti University

1 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

What is life: The physical aspects of the living cell

• Order emerges from disorder
• Mutations are quantum leaps
• Negative entropy is the source of

non-equilibrium state of living systems

• An aperiodic crystal is the

physical basis of heredity

• The living systems do not elude

the “laws of physics”

2 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Are biological systems also physical systems?

Yes for Schrödinger as a physicist! Since “in principle” every structure or event in a living system obeys the known laws of physics But, in practice how this “in principle” understanding may help for “actual” understanding?

3 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

The anatomy of the physical “understanding”

• Every physical system must be

decomposed into subsystems

• The nature of the interactions of

subsystems must be deduced

• The state of physical system is

derived from these two elements

• The evolution (usually time-

dependent) of the state of system governs a physical law

• When all these are available, we have

a physical model

• Solar system as a classic example

4 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

The “effective” understanding in physics

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• Physical system may be decomposed

into various types of subsystems

• The nature of the interactions are

different for various decomposition schemes

• Usually there is a decomposition scheme

that is perceived to be effective

• Everything redundant has been

discarded from the effective model

• There is a hierarchical structure in

model building

• The kinetic theory of gases is a classic

example

Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

What “in principle” is not yet understandable

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• There are systems or events that the

physical laws governing their evolution is not yet known

• The particle physics at ultrahigh

energies

• The internal structure of the back holes
• The start of the universe some
• The nature of dark matter
• The nature of dark energy
• Search in underlying theories is
• ngoing in these areas though they

govern phenomena much beyond the everyday life and probably irrelevant to biology…

Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

What is not yet understandable “effectively”

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• There are systems or events that the laws

(physical theories) governing their evolution is known, but the effective modeling has not yet been achieved

• The mechanism behind high-temperature

superconductivity and the nature of turbulence in hydrodynamics are examples

• Searching effective models is ongoing in

these areas…

• In principle understating does not guarantee

effective understating and without the latter, physicists are not usually claiming a physical” understanding

Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Are biological systems also physical systems?

Conditional yes! If we are able to construct “effective models” for various types of biological systems

8 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Theories of complexity: Effective biological modeling

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• Extending the model construction business

to biology: Theoretical and computational biology

• Computational neuroscience
• Genetic population
• System biology
• Modeling ecological systems
• Network biology
• Modeling immunological system
• Searching effective models is ongoing in

various areas of biology: From the molecular biology to the biology of ecosystems

Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

How successful are current effective models in biology?

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• In some areas, like neurobiology, the effective

models have been quite efficient

• In other areas, like the origin of life at the Earth, or

the evolution of the global ecosystem of the Earth, things are less clear…

• Are there inherent limitations to the biological

modeling?

Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Take home lesson: What I can model, I understand

Let’s make a pause and take a twist!

11 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Are biological systems also chemical systems?

Strange question! Isn’t true that chemical systems are just a small subset of the physical systems? Let’s look at the problem from an alternative viewpoint!

12 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

The anatomy of the “understanding” in chemistry: Molecular structures

• Every chemical system is

composed of molecules, they are the natural units of chemistry

• Each molecule has a molecular

structure, which is code for the constituent atoms and the chemical bonds linking them

• Every chemical phenomena, like a

chemical reaction, is finally conceived as a transformation of molecular structures

13 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

The anatomy of the “understanding” in chemistry: Chemical synthesis

• Every reasonable molecular

structure drawn on a paper is a potential chemical system

• Every potential chemical

system is realized in laboratory starting from known simple molecular structures and using chemical reactions to reach more complex molecular structures

• The procedure is called the

chemical synthesis

• The synthesis of complex

natural products is an example

14 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

The new dimension of the chemical synthesis: “Creation”

• From the space of all molecular

structures not all have been realized in nature

• The ultimate goal of the chemical

synthesis is realizing all potential molecular structures as actual chemical systems

• In this procedure new chemical

systems are materialized without no previous known existence in nature

• The art of chemical synthesis is

the de novo creation…

15 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

The chemical synthesis as the “chess” game of chemistry

• To start the game of chess you must know all the

pieces and the rules governing their moves

• However, what makes the chess an intellectual

game is the strategies used for winning

• The known molecules and reactions are the pieces
• f the synthetic chemist and it is an intellectual

game for him/her to design strategies for synthesizing a new complex molecule

• The grandmasters of chemistry are whom able to

make new plans to climb in the space of molecular structures, they understand chemistry…

16 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Take home lesson: What I can create, I understand

• r

What I cannot create, I do not understand last words of Richard Feynman (15 February 1988), recalled by his sister!

17 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Are biological systems also chemical systems?

Conditional yes! If we are able to reconstruct biological systems from their constituent molecules and more, if we may “design” novel biological systems without any previous existence…

18 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Synthetic biology starts when descriptive biology stops…

19 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

A reductionist view to biology

• Cells are the basic units of living things
• Cells contains Organelles
• Organelles are assemblies of large

complex biomolecules

• Biomolecules, i.e., DNA, RNA and

proteins, are composed of mainly simple organic molecular building blocks

• These building blocks are themselves

made mainly from carbon, hydrogen,

• xygen, nitrogen, sulfur, phosphorus,

… atoms

• In the end, a cell is a highly organized

assembly of atoms

20 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

What is the synthetic biology?

• There is no consensus on its exact

definition!

• Let’s try one similar to that of the

chemical synthesis

• Synthetic biology is any attempt to

synthesis chemically the existing units of the cell, at the level of large biomolecules or more complex units, from scratch or designing completely novel units integrable within the existing cells with clear biological functions

21 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Let’s have a brief look on Craig Venter’s enterprise as an illustrative example

22 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Chemical synthesis of the whole genome of a bacteria

• M. genitalium has the smallest

genome consisting of 582’970 base pairs (482 protein coding genes)

• In 2007 the whole DNA was

synthesized chemically and then inserted into a cell

• The resulting synthetic organism

was an exact copy of the natural

• rganism

Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016) 23

“Transforming” a species into other by the synthetic genome

• The genome of M. mycoides was

chemically synthesized and then transplanted into M. capricolum containing its own genome

• The new genome then takes the

control of the guest cell and M. capricolum transformed into M. mycoides

• In Venter own words: “Changing

the software completely eliminated the old organism and created a new

• ne”

Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016) 24

“Designing” a new species

• The genome of M. mycoides was

modified and only those found essential were retained (473 genes)

• The new synthetic organism was

called JCVI-syn3.0

• The genome not only contains

essentials genes but the name of authors of the paper in the form of genetic codes!

• This new species has the smallest

known genome and is a manifestation of the minimal cell concept important for the origin of life conundrum

Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016) 25

Some implication of the synthetic biology

26 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

From biology to philosophy: Against vitalism

• In the most of the human history an

impenetrable barrier is assumed between the animate and inanimate worlds

• In the dawn of 19 century it was assumed

that organic molecules are the basis of distinction, having a distinct quality and producible only by living things

• This is the basis of the so-called vitalism
• The synthesis of urea and acetic acid in

1828 and 1845 by Wohler and Kolbe from purely inorganic precursors undermined the distinction between

• rganic and inorganic molecules

27 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Synthetic biology: Against “neo-vitalism”?

• Living cells have a distinct complex
• rganization irreducible to their constituent

molecules

• In the start of 20 century it was assumed

that this irreducible complexity makes living things distinct from non-living

• bjects
• Is synthetic biology, at the dawn of 21

century, now starts to penetrate the final perceived barrier between the animate and inanimate worlds?

• Is the total synthesis of a living cell viable?

28 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

What is life: Beyond Schrödinger…

• Life is…
• From the space of all living things not all have

been realized in nature

• The ultimate goal of the synthetic biology is

realizing all potential living things as actual biological systems

• In this procedure new biological systems will

be materialized without no previous known existence in nature

• The ultimate art of the synthetic biology is the

de novo creation of life…

• And, yet the living systems do not elude the

“laws of physics” as Schrödinger conceived…

29 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)

Thanks for your patience and attention

30 Prepared by Shant Shahbazian for the seminar of "What is life" at the Institute for research in fundamental sciences (IPM) (2-Nov-2016)