Perkembangan Biologi Molekuler dan Pembelajarannya Sutiman B. Sumitro Laboratorium Biologi Sel dan Molekuler Fakultas MIPA Universitas Brawijaya sutiman@ub.ac.id

Pengetahuan Ilmiah dilakukan dengan berpikir runtut bersifat analitik dan sintetik. Kebenaran Ilmiah adalah keselarasan pikiran dengan hasil pengamatan obyek yang bersifat inderawi (mata, telinga, rabaan, penciuman) Obyek komplek dalam biologi dipelajari dengan cara mengurai dari obyek besar dan komplek ke bagian-bagian yang lebih kecil. Dilakukan upaya penyederhanaan dan fokus untuk dapat dibahas dan dipahami, mencari bukti, bersifat linier dan logis

Disiplin Ilmu diklasifikasikan berdasarkan cara pendekatan berfikir Biologi Klasik: Berbasis Morfologi Ekologi: Berbasis populasi Biologi Modern Berbasis Seluler dan Molekuler Holism Reduksionistik Molecular and Cellular Biology, Genetic engineering, Modern Medical sciences, etc. Ada kecenderungan parsialisme yang harus disikapi dengan kehati-hatian

Reductionist approach 12 April 2017 www.divinecigarette.com

The linear causal pathway implied in the central dogma of molecular biology. The epigenetic control pathway of gene expression as circular (including bidirectional causal influences) and dynamic (open to environment). F Mazzocchi . WIREs Syst Biol Med 2012. DOI: 10.1002/wsbm.1181, Copyright © 2012 Wiley Periodicals, Inc. 5

Integrative Bioinformatics diperlukan karena fakta berikut: Perkembangan cepat data bidang biologi molekuler akibat dari penggunaan teknologi genomik: Microarray, NGS, NMR, mass spectrometry, protein chips, gel electrophoresis data, Yeast-Two-Hybrid, QTL mapping, gene silencing, and knockout. Bantuan teknik2 tersebut telah menghasilkan ribuan data, bahkan tidak jarang banyak sekali data meskipun berasal hanya dari satu kegiatan eksperimen Data Biologis tersebar di berbagai data base dan ratusan jurnal ilmiah Semua ini perlu didayamanfaatkan baik melalui model, integrasi informasi untuk menghasilkan informasi yang lebih benar sesuai dengan kenyataan berupa siostem biologi yang komplek .

Sifat Reduksionistik bidang kajian Biologi Sel-Molekuler Reductionism contain so many simplification and assumptions which generate misinterpretation Versus Complexity Science The emerging complexity science in respond to the disadvantage of reductionism in studying complex phenomena such as living system

What is Complexity Science? Complexity science is a broad term for understanding a range of complex phenomena. If we break down a ‘complicated’ system into its basic components and analyze how the components behave, we can recreate the behavior of the whole system by running all the components together. There are a wide variety of ‘complex’ scientific and engineering problems though defying this type of analysis. The behavior of a complex system is an emergent property of the interactions of the components. Seth Bullock, 2006

Physic is the origin of Complexity Science Complexity theory developed from the physical sciences in the mid-20th century. It is argued that the world is made up of interwoven orderly, disorderly, and complex parts. Rigid rules and laws help to explain orderly phenomena, but are limited in predicting the behavior of complex phenomena. Complexity science recognizes the strengths of the orderly Newtonian framework while tackling the unpredictability of complex and disorderly phenomena. Seth Bullock, 2006

The contribution of reductionist and holistic (antireductionist) methodologies to the mechanistic explanation of increasing complex biological phenomena. The kind (linear or nonlinear) of process is illustrated in the lower x-axis. The kind of system the processes are part of (aggregative, component, or integrative) is indicated in the middle x-axis. The degree of biocomplexity of biological phenomena is ranked in the upper x-axis (number 1–11). The left and right y-axis portray the contribution (in percentages) of reductionist and holistic methodologies, respectively, to a research program aiming to mechanistically explain a biological phenomenon exhibiting a given degree of complexity. (Reprinted with permission from Ref 26. Copyright © 2002 Taylor and Francis Ltd., http://www.tandfonline.com) F Mazzocchi . WIREs Syst Biol Med 2012. DOI: 10.1002/wsbm.1181, Copyright © 2012 Wiley Periodicals, Inc. 11

Apa yang harus dilakukan?

Kompleksitas Sistem Makro Molekul di Dalam Sel (Dicirikan oleh fenomena “self assembly” dan “kecerdasan”) Nucleosome

Set of Human Chromosomes Nano meter (nm) size chromatin filaments Mikrometer (µm) Set of Human Chromosomes Nano meter (nm) size chromatin filaments (sepermiliar meter) Mikrometer (µm) Size Cromosomes (sepersejuta meter)

All creatures can be describe as atomic, an angle to view living system Where is the ideas of performing life is located?

Nano Science Modern Physics Quantum Physics Newtonian Atom and Subatomic, particles Time and space less Newtonian Gravitation, speed Space and time Measurable dimension, weigh, and speed Functional Structures of biological molecules are within this range 1 nm 100 nm

Electricity and Magnetism in Biological Molecules Energy generation to build complex structure of organic chemical compounds is based on their physical and chemical characters Electrical properties of Biological molecules can conduct electricity and influence development of molecular electronic (Porath, et al., 2004) DNA and other biological macromoleculs behave as an isolator, semiconductor, conductor or superconductor depending on the surounding molecules or the medium (Braun et al., 1998; Pablo et al., 2000; Zang et al., 2002; Storm et al., 2001; Porath et al., 2005; rakitin et al., 2001; Cohen et al., 2005) These Biological molecules perform electronic transport and have magnetic phenomena (Zong et al., Eds, 2003)

The phonon in twisting and stetching modes of DNA (Müller et al., 2002) Phonon is collective exitation in a periodic, elastic arrangement of atoms or molecules in condensed matters, represents exited state in quantum mechanical quantization of modes of vibrations of elastic structures of interacting particles (Igor Tamm, 1932).

Magnetic in moving electron Paramagnetic Unpaired electron 2p Diamagnetic Paired electron 21 21 21 7.8

Biradical and magnetism Edward Kosower (1967) proposed an idea of biradical in an aromatic organic compounds. Each of which having unpaired electrons. The magnetic force of this compound used for making agregation.

Large electron density Aromaticc Phenantren Structures Rich of Electron Moving on Its Surface * UV H2O* H• + •OH OH Negative Fragment Kosower (1968) P• P • P P P P diamagnetic Paramagnetic n P• P• P P P P P P Large electron density www.smartbio.org

Mobile Electron in associated HO• cyclohexadienyl * solar ⁺˙OH Solar Biradical Phenanthrene Phenanthrene* * solar Biradical ⁺˙OH 1,2-Benzanthracene 1,2-Benzanthracene* * Biradical ˙OH Chrysene Chrysene* Balur Org

Atomic level and subatomic At atomic level ,matter has dual aspect ,it appears particles and waves The packets quanta in “cage” volume varied 2n, depends on the distance of each quanta density Light is emitted and absorbed in the form of “quanta” or photons, when travel through space they appear as vibrating electric and magnetic fields, which show all character behavior of waves. Electrons, considered to be particles, when a beam of these particles, is sent to slit it is diffracted just like a beam of light, ---- in other words electrons, too, behave like waves a particle a wave Energy packets “quanta” Varied waves

Proses Hidup dan Molekul Komplek Heme A complex as a substance composed of two or more components capable of an independent existence. A coordination complex is one in which a central atom or ion is joined to one or more ligands through what is called a coordinate covalent bond in which both of the bonding elecrons are supplied by the ligand. In such a complex the central atom acts as an electron-pair acceptor Cytochrome-c

Hemoglobin Catalase Myoglobulin Cytochrome-c

Heme of red blood hemoglobin A compound formed by union of a metal ion (usually a transition metal ) with a non metallic ion or molecule called ligand or complex agent Heme of red blood hemoglobin Iron's oxidation state in oxyhemoglobin Assigning oxygenated hemoglobin's oxidation state is difficult because oxyhemoglobin (Hb-O2), by experimental measurement, is diamagnetic (no net unpaired electrons), yet the low-energy electron configurations in both oxygen and iron are paramagnetic (suggesting at least one unpaired electron in the complex). Albert et al., 2007

The whole is greater and smarter than the sum of the parts Complex compound  or Coordination compound (in atomic language) Complex ion:   Anions which has a molecular structure consisting of a central atom bonded to other atoms by coordinate covalent bonding The notion of a complex system is distinguished from that of complicated system, which is more than the sum of its parts.

Ringkasan Pembicaraan Biologi Sel dan Biologi Molekuler telah mencapai akumulasi pengetahuan dari hasil riset yang sangat banyak Mendorong setiap kegiatan penelitian dilakukan dengan tingkat spesialisasi yang menjadi sangat spesifik Hasil kajian-kajiannya tersebar dalam ratusan publikasi di jurnal-jurnal ilmiah setiap minggunya, menyulitkan seseorang untuk melngikutinya secara manual Bahan ajar terus berkembang sehingga memerlukan updating terus menerus dengan intensitas tinggi sehingga cenderung makin lama-makin terasa menyulitkan Perlu bantuan bantuan sistem kerja in silico berupa mekanisme akses ke basis penyimpanan data ilmiah melalui sistem jejaring kerja sistem informasi dan sistem piranti lunak untuk memudahkan seseorang membangun hipotesis dengan pengetahuan terkini.

Water Diamagnitism Levitating frog