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The GECKIL Genetic Engineering Laboratory

The Vitreoscilla hemoglobin

(# 1 modulator in metabolic engineering)

The Vitreoscilla hemoglobin (commonly abbreviated as VHb) was first discovered by Dale A. Webster in 1986 (1). However, Dale (latter to be my co-advisor together with Benjamin C. Stark, both at IIT, Chicago) originaly discovered it in 1966 (2) and given its prevalent presence in the cytoplasm but not in the membrane fraction, he named it as "the soluble form of the cytochrome bo", the terminal oxidase of bacterial respiratory chain.

I had the privilege to be one of the firsts to study the VHb and its gene (vgb) with Dale and Ben. Ben has also been known for his discovery of "catlytic RNA" during his postdoc study at Yale University, securing the Nobel Prize in Chemistry in 1989 for his advisor Sydney Altman. Having the opportunity to work with such high-caliber scientists was the most revarding part of my life with science. Robert M. Roth, then the chairman of the Biology Department, was another mentor whom I liked how he orchestrated his teaching with an explicit Brooklyn accent. Thank to all three for believing in me, a naive Turkish native, to be their TA for their courses (Advanced Biochemistry by Dale, Molecular Cell Biology by Ben, and Microbial Genetics and Genetic Engineering by Bob).

For sometime, the hemoglobins were considered to be the proteins of only eukaryotic origin. The main reason for this view is that, most eukaryotic organisms (with the exeption of the single celled ones) are multicellular and the free diffusion of oxygen into cells deep in the thick tissues and organs would not be possible without a suitable carrier (i.e. hemoglobin). Now, we know that hemoglobins exisit virtually in all kingdoms of life. But, what role such proteins may play in free living single cells, such as bacteria, which acquire oxygen from the environment readily through passive diffusion. Although, this is a question of ongoing debate, we now also know that not only do these ubiquitous protiens transport the oxygen between tissues, the known function of hemoglobins, but also they play other roles ranging from intracellular oxygen transport to catalysis of redox reactions.

Aerobic (oxygen using) organisms started to dominate the life on earth about 3 billion years ago, as the anoxic (oxgen-free) atmosphere become more and more oxic (oxygenated) with the advent of photosynthesis about 4 billion years ago. With some minor exeptions (e.g., anerobic bacteria), today life on earth in all levels, as we know it, is oxygen dependent and it is no surprise that many genes (if not all) in all these life forms from bacteria to human are directly or inderectly regulated by oxygen. Moreover, oxygen is the final electron acceptor in the respiratory chain which is coupled to oxidative phosphorylation through which all organisms generate about 90 % of thier energy (i.e., ATP). So without this gas, i.e., oxygen, life as a whole would be succumed to death.

In multicellular organsims with bulky bodies, oxygen transfer into the cells residing far from perifery would be a problem if not solved by a specilized carrier. Because, oxyen is easly disolved in cellular and extracellular milieu where many oxygen hungry molecules or reactions can readly consume it, hindering its further transfer. Life solved this problem by creating hemoglobins and veins. The tracks, that are veins, provide blood cells (i.e. erythrocytes) which carry oxygen loaded hemoglobin to their destination all over the body (when there is no gain to oxygen, ther is pain!). With its highly efficient oxyen-carbon dioxyde affinity kinetics, hemoglobin relaeses more oxygen to regions where there is much need (low oxygen, high carbondioxide regions).

A bacterium is both an organism and also a cell. It is not in tissue form and does not have extensive intracellular structures (i.e., organeles). As for the cells in organisms, oxygen is easly diffuesed through its membrane and the final destinations are not that far when its size is considered (~1 x 2 µm). So, why invest so much energy to synthesize a 146 amino asit long hemoglobin protein (who knows how many molecules of it).

The term "metabolic engineering" was first coined by late James E. Bailey (then at Caltech) and Gregory Stephanopoulos (Massachusetts Institute of Technology (MIT)) in 1991 in the same issue of the journal Science (3,4). Prof. Bailey was also a pioneer in VHb studies (and his group was a rival of our laboratory at IIT) and Prof. Stephanopoulos is the editor-in-chief of the journal Metabolic Engineering.

The main focus of The GECKIL Genetic Engineering Laboratory involves isolation, cloning, and regulation of bacterial genes expressing products of high industrial importance. An anticancer enzyme, L-asparaginase, produced only by certain bacteria and L-dopa and dopamine, the drugs used in Alzheimer’s and Parkinson diseases are the main products under the investigation. The laboratory has also a long standing interest in Vitreoscilla hemoglobin (VHb), the first bacterial hemoglobin. The emphasis is to understand how the presence of this protein in heterologoues bacteria affects the physiological and biochemical characteristics at the molecular level. Furthermore, the up-regulation of Vitreoscilla hemoglobin gene (vgb) under microaerobic conditions make this protein a highly suitable agent for bioprocesses requiring a critical level of oxygen. As the production of L-asparaginase, L-dopa, and dopamine are highly regulated by the availability of oxygen, the application of the VHb in their production may prove advantageous.
 
In this endevaour, our studies showed that in certain heterologoues bacteria (bacteria which do not have the vgb gene naturally) VHb causes almost an order of magnitude (i.e., 10-fold) higher oxygen uptake and utlization rate than the vgb- host strains, resulting severe metabolic perturbations and pysiological effects (e.g., cell growth, increased viabilty in solvent containing growth media)5-11.
 
RESEARCH IN OUR LABORATORY

Genetic Engineering of Vitreoscilla Hemoglobin Gene

  • Cloning, expression and effect of Vitreoscilla hemoglobin gene in industrially important microorganisms
  • Oxidative stress and antioxidant properties of bacteria genetically engineered with Vitreoscilla hemoglobin gene©
  • Potential use of Vitreoscilla hemoglobin in bioremediation
  • Production of industrially important fermantative solvents through the use of Vitreoscilla hemoglobin©
  • Use of Vitreoscilla hemoglobin for the enhancement of production of L-asparaginase: an enzyme used in cancer therapy©
  • Metabolic engineering: secondary metabolite flux distribution in Erwinia herbicola  expressing Vitreoscilla hemoglobin gene©

Metabolic Reprogramming and Cancer

  • mTOR signal pathway in human cancers
  • Ghrelin and Cell Physiology

Bioprocess Engineering

  • Development of methods for bioprocessing of products with high therapeutic value
  • Bacterial synthesis of L-DOPA and DOPAMINE [(Cloning, isolation, expression of the genes (Tyrosine phenol lyase and dopaminedecarboxylase) for L-DOPA and DOPAMINE production in bacteria)].

1. Wakabayashi, S.; Matsubara, H.; Webster, D. A., Primary Sequence of a Dimeric Bacterial Hemoglobin from Vitreoscilla. Nature 1986, 322, (6078), 481-483.

2. Webster, D. A.; Hackett, D. P., The purification and properties of cytochrome o from Vitreoscilla. J Biol Chem 1966, 241, 3308-3315.

3. Bailey, J. E., Toward a Science of Metabolic Engineering. Science 1991, 252, (5013), 1668-1675.

4. Stephanopoulos, G.; Vallino, J. J., Network Rigidity and Metabolic Engineering in Metabolite Overproduction. Science 1991, 252, (5013), 1675-1681.

5. Geckil, H.; Stark, B. C.; Webster, D. A., Cell growth and oxygen uptake of Escherichia coli and Pseudomonas aeruginosa are differently effected by the genetically engineered Vitreoscilla hemoglobin gene. Journal of Biotechnology 2001, 85, (1), 57-66.

6. Geckil, H.; Gencer, S.; Kahraman, H.; Erenler, S. O., Genetic engineering of Enterobacter aerogenes with theVitreoscilla hemoglobin gene: cell growth, survival, and antioxidant enzyme status under oxidative stress. Research in Microbiology 2003, 154, (6), 425-431.

7. Geckil, H.; Barak, Z.; Chipman, D. M.; Erenler, S. O.; Webster, D. A.; Stark, B. C., Enhanced production of acetoin and butanediol in recombinant Enterobacter aerogenes carrying Vitreoscilla hemoglobin gene. Bioprocess and Biosystems Engineering 2004, 26, (5), 325-330.

8. Erenler, S. O.; Gencer, S.; Geckil, H.; Stark, B. C.; Webster, D. A., Cloning and expression of the Vitreoscillahemoglobin gene in Enterobacter aerogenes: Effect on cell growth and oxygen uptake. Applied Biochemistry and Microbiology 2004, 40, (3), 241-248.

9. Geckil, H.; Gencer, S., Production of L-asparaginase in Enterobacter aerogenes expressing Vitreoscillahemoglobin for efficient oxygen uptake. Applied Microbiology and Biotechnology 2004, 63, (6), 691-697.

10. Kurt, A. G.; Aytan, E.; Ozer, U.; Ates, B.; Geckil, H., Production of L-DOPA and dopamine in recombinant bacteria bearing the Vitreoscilla hemoglobin gene. Biotechnology Journal 2009, 4, (7), 1077-88.

11. Erenler, S.; Geckil, H., Cloning, isolation and expression of L-asparaginase gene (ansB) in different gram-negative bacteria expressing Vitreoscilla hemoglobin. Current Opinon in Biotechnology 2011, 22, S118-S118.


Periodic Table of the People


PhD Standards (Turkish)

ACADEMIC SUPERVISING

  • M.S., Şebnem O. Erenler (2002); Effect of the bacterial hemoglobin gene on physiological and metabolic activities of Enterobacter aerogenes; Department of Biology, Inonu University.
  • M.S., Nafia C. Ateş (2003); Production of fermentative products and solvent tolerance by Enterobacter aerogenes carrying the Vitreoscilla hemoglobin gene; Department of Biology, Inonu University.
  • Ph.D., Hüseyin Kahraman (2004); Potential use of Pseudomonas aeruginosa in bioremediation using a genetically engineered Vitreoscilla hemoglobin gene; Department of Biology, Inonu University.
  • M.S., Salih Gencer (2004); Vitreoscilla hemoglobin geni klonlanmış bakterilerde L-asparaginaz enziminin sentezi: önemeli bir kanser kemoterapi ajanı; Department of Biology, Inonu University
  • M.S., Mirac Uckun (2006); Screening of random mutagenised Gram-negative bacterial strains for high level L-asparaginase production; Department of Biology, Inonu University.
  • M.S., Ufuk Özer (2006); Dopamine synthesis in bacteria; Department of Biology, Inonu University
  • Ph.D., Burhan Ateş (2007);(Co-advisor) Production, chemical characterization and some clinical applications of anticancerogenic L-asparaginase from various Gram-negative bacteria; Department of Chemistry, Inonu University.
  • Ph.D., Şebnem O. Erenler (2007); Cloning, isolation and expression of L-asparaginase gen (ansB) in Gram-negative bacteria. Department of Biology; Inonu University.
  • M.S., Emel Aytan (2009); Production of L-DOPA in Erwinia herbicola bearing the Vitreoscilla hemoglobin gene; Department of Biology, Inonu University
  • M.S., Salih Gencer (2009); The Effect of Oxidative Stress and RNA interferance on Expression of Matrix metalloproteinase genes (MMPs) in Gastric Cancer; Department of Molecular Biology and Genetics, Fatih University, Istanbul
  • Ph.D., Aslı Giray Kurt (2012); Vitreoscilla Hemoglobininin Erwinia herbicola’da İkincil Metabolit Akış Dağılımı Üzerine Etkisi; İnönü Üniversitesi, Biyoloji Bölümü

ACADEMIC SUPERVISING (ongoing...)

  • Ph.D., Veyis Selen (2008 -); Simultaneous synthesis of L-DOPA and dopamine using recombinant microorganisms, Department of Chemical Engineering, Firat University
  • Ph.D., Emel Aytan (2013- ); Role of mTOR signal pathway in cell growth and cancer
  • Ph.D., Özgür Yılmaz (2013 -); Thesis subject not determined yet.  Department of Biology, Inonu University

ALUMNI

  • Şebnem Özalp Erenler, an alumna (MS'02, PhD'07) of my lab, is now an Assistant Professor in the Department of Biology, Inonu University
  • Burhan Ateş, an alumnus (PhD'07) of my lab, is now an Associate Professor in the Department of Chemistry, Inonu University
  • Hüseyin Kahraman, an alumnus (PhD'04) of my lab, is now an Associate Professor in Department of Biology, Inonu University
  • Miraç Uçkun, an alumnus (MS'06) of my lab, is now an Assistant Professor in the Department of Biology at Adıyaman University, Adıyaman, Turkey
  • Salih Gencer, an alumnus (MS'04, PhD'09) of my lab, is now a postd-doctoral reserach associate in the Department of Biochemistry and Molecular Biology at the Medical School of South Carolina
  • Ufuk Özer, an alumnus (MS'06) of my lab, is now a Postdoctoral Fellow in the Department of Biology at the Universty of South Carolina
  • Nafia Canan Ateş (Gürsoy), an alumna (MS'03) of my lab, is now in Medical School at Inonu University
  • Venhar Celik, an alumna (postdoc'09) of the GECKIL GENETIC ENGINEERING LABORATORY, is now a Postdoctoral Fellow in the Department of Bioengineering at University of Illinois, Urbana-Champaign, Il, USA.
  • Irmak Icen, an alumna (part of doctoral study'09) of the GECKIL GENETIC ENGINEERING LABORATORY, is now a Postdoctoral Fellow in the Department of Bioengineering at University of Illinois , Urbana-Champaign, Il, USA.
  • Züleyha Türkoğlu (Almaz) (Reserach Assistant at the Department of Molecular Biology and Genetics, Muş Alparslan University)

UNDERGRADS

  • Elif Sakız, Elif Sakız, an undergraduate from the Department of Molecular Biology and Genetics at Yeni Yüzyıl University (Istanbul), was a summer (2014) intern in my laboratory. Her project involved the cloning and effect of Vitreoscilla hemoglobin gene in Deinococcus radiodurans, a highly radio-resistant bacterium subjected to NASA research.
  • Ferhat Öçal, an undergraduate from the Department of Chemistry at Abant İzzet Baysal University (Bolu), was a summer (2015) intern in my laboratory. His project involved the cloning of chondroitin genes in heterologoues bacteria.

Ph.D. Standards

P-31: Mehta R, Geckil H, Gozuacik D.
Editorial (Cancer: normal cells' reply to a deadly fate)
Turkish Journal of Biology, 38, (2014), i

P-30: Erenler AS and Geckil H.
Triumph or tragedy: progress in cancer.
Turkish Journal of Biology, 38, (2014), 701-707

Issue Editors
Rajendra Mehta (Illinois Institute of Technology), Hikmet Geçkil, Devrim Gözüaçık (Sabancı University)
P-29: Erenler SO and Geckil H.
Effect of Vitreoscilla Hemoglobin and Culture Conditions on Production of Bacterial l-Asparaginase, an Oncolytic Enzyme.
Applied Biochemistry and Biotechnology, 2014,173,8,2140-2151
 
   
P-28: Demirci U and Geckil H.
Editorial: Micro and nanofluidics – applications in biotechnology. 
Biotechnology Journal, 2011; 6(2): 131
 
P-27: Gurkan UA, Moon S, Geckil H, Xu F, Wang S, Lu TJ and Demirci U.
Miniaturized lensless imaging systems for cell and microorganism visualization in point-of-care testing. 
Biotechnology Journal, 2011; 6(2): 138-149.
 
 
 
 
 

 

Issue Editors
Utkan Demirci (Harvard University) and Hikmet Geckil

 
P-26: Geckil H, Xu F, Xiaohui Z, Moon S-J, Demirci U.
Engineering hydrogels as extracellular matrix mimics.
Nanomedicine, 2010; 5(3): 469-484.
 
P-25: Geckil H and Calik P. 
Editorial: Biotech in Turkey. 
Biotechnology Journal, 2009 4(7), 951.
 
P-24: Kurt AG , Aytan E, Ozer U, Ates B and Geckil H
Production of L-DOPA and dopamine in bacteria bearing Vitreoscilla hemoglobin gene.
Biotechnology Journal2009 4(7), 1077-1088.
Issue Editors
Hikmet Geckil and Pinar Calik (Middle East Technical University)
P-23: Aydin S, Karatas F and Geckil H.
Simultaneous Quantification of Acylated and Desacylated Ghrelin in Biological Fluids.
Biomedical Chromatography, 20008; 22(12): 1354-1359.

P-22: Aydin S, Geckil H, Kilic N, Erman F, Kilic SS and Yesilada O.
Is Ghrelin a Natural Anti-Microbial Agent?
Turkish Journal of Medical Sciences, 2008; 38(2): 187-187.

P-21: Aydin S, Geckil H, Karatas F, Donder E, Kumru S, Kavak EC, Colak R, Ozkan Y, Sahin I.
Milk and blood ghrelin level in diabetics.
Nutrition, 2007; 23(11-12): 807-811.

P-20: Aydin S, Ozercan IH, Geckil H, Dagli F, Aydin S, Kumru S, Kiliç N, Sahin I, Ozercan MR.
Ghrelin is present in teeth.
Journal of Biochemistry and Molecular Biology, (2007); 40(3):368-372.

P-19: Aydin S, Geckil H, Karaoglu A, Elkiran ET.
Ghrelin: A novel peptide with therapeutic effect in certain cancers?
Medical Hypotheses, (2007); 69(5): 1157-1158.

P-18: Geckil H, Gencer S, Ates B, Ozer U, Uckun M, Yilmaz I.
Effect of Vitreoscilla hemoglobin on production of a chemotherapeutic enzyme, L-asparaginase, by Pseudomonas aeruginosa.
Biotechnology Journal, (2006); 1(2): 203-208.
 
P-17: Aydin S, Ozercan HI, Aydin S, Ozkan Y, Dagli F, Oguzoncul F, Geckil H.
Biological rhythm of saliva ghrelin in humans.
Biological Rhythm Research, (2006); 37(2): 169-177.
 
P-16: Aydin S, Geckil H, Zengin F, Ozercan HI, Karatas F, Aydin S, Balik DT, Ozkan Y, Dagli F, Celik V.
Ghrelin in plants: What is the function of an appetite hormone in plants?
Peptides, (2006); 27(7): 1597-1602.
 
P-15: Kahraman H and Geckil H.
Degradation of benzene, toluene and xylene by Pseudomonas aeruginosa engineered with the Vitreoscilla hemoglobin gene.
Engineering in Life Sciences, (2005); 5(4): 363-368.
 
P-14: Geckil H, Ates B, Durmaz G, Erdogan S, Yilmaz I.
Antioxidant, free radical scavenginging and metal chelating characteristics of propolis.
American Journal of Biochmemistry and Biotechnology, 2005; 1(1): 27-31.
 
P-13: Geckil H, Ates B, Gencer S, Uckun M, and Yilmaz I.
Membrane permeabilization of Gram-negative bacteria with a potassium phosphate/hexane aqueous phase system for the release of L-asparaginase: an enzyme used in cancer therapy.
Process Biochemistry, 2005; 40(2): 573-579.
 
P-12: Geckil H, Barak Z, Chipman DM, Erenler SO, Webster DA and Stark BC.
Enhanced production of acetoin and butanediol in recombinant Enterobacter aerogenes carrying Vitreoscilla hemoglobin gene.
Bioprocess and Biosystems Engineering, 2004; 26(5): 325-330.

P-11: Geckil H, Arman A, Gencer G, Ates B and Yilmaz HR.
Vitreoscilla hemoglobin renders Enterobacter aerogenes highly susceptible to heavy metals.
Biometals, 2004; 17(6): 715-723.

P-10: Geckil H, Gencer S and Uckun M.
Vitreoscilla hemoglobin expressing Enterobacter aerogenes and Pseudomonas aeruginosa respond differently to carbon catabolite and oxygen repression for production of L-asparaginase: an enzyme used in cancer therapy.
Enzyme and Microbial Technology, 2004; 35(2-3): 182-189.

P-09: Ates B, Yilmaz I, Geckil H, Iraz M, Birincioglu M, Fiskin K.
Protective role of melatonin given either before ischemia or prior to reperfusion on intestinal ischemia-reperfusion damage.
Journal of Pineal Research, 2004; 37(3): 149-152.

P-08: Geckil H and Gencer S.
Production of L-asparaginase in Enterobacter aerogenes expressing Vitreoscilla hemoglobin for efficient oxygen uptake.
Applied Microbiology and Biotechnology, 2004; 63(6): 691-697.

P-07: Erenler SO, Gencer S, Geckil H, Stark BC, and Webster DA.
Cloning and expression of the Vitreoscilla hemoglobin gene in Enterobacter aerogenes: effect on cell growth an oxygen uptake.
Applied Biochemistry and Microbiology, 2004; 40(3): 288-295.

P-06: Geckil H, Gencer S, Kahraman H, and Erenler SO.
Genetic engineering of Enterobacter aerogenes with Vitreoscilla hemoglobin gene: cell growth, survival, and antioxidant enzyme status under oxidative stress.
Research in Microbiology, 2003; 154(6): 425-431.

P-05: Munzuroglu *, Karatas F, and Geckil H.
The vitamin and selenium contents of apricot fruit of different varieties cultivated in different geographical regions.
Food Chemistry, 2003; 83(2): 205-212.

P-04: Munzuroglu O, Obek E, and Geckil H.
Effects of simulated acid rain on the pollen germination and pollen tube growth of apple (Malus sylvestris Miller cv. Golden).
Acta Biologica Hungarica, 2003; 54(1): 5-103.

P-03: Yurekli F, Geckil H, and Topcuoglu F.
The synthesis of indole-3-acetic acid by the industrially important white-rot fungus Lentinus sajor-caju under different culture conditions.
Mycological Research, 2003; 107(3): 305-309.

P-02: Munzuroglu O and Geckil H.
Effects of metals on seed germination, root elongation, coleoptile and hypocotyl growth in Triticum aestivum and Cucumis sativus.
Archives of Environmental Contamination and Toxicology, 2002; 43(2): 203-213.

P-01: Geckil H, Stark BC, and Webster DA.
Cell growth and oxygen uptake of Escherichia coli and Pseudomonas aeruginosa are differently affected by the genetically engineered Vitreoscilla hemoglobin gene.
Journal of Biotechnology, 2001; 85(1): 57-66. 
 
PUBLISHED CONFERENCE PROCEEDINGS
Icen I, Celik V, Pelle R, Aytan E, Munzuroglu O, Geckil H.
Isolation, cloning and sequence analysis of gene encoding the lactate dehydrogenase enzyme from Theileria parva.                            
FEBS JOURNAL, 2011, 278, 329.
 
Celik V, Icen I, Pelle R, Kurt AG, Munzuroglu O, Geckil H.
A new candidate for antitheilerial target: isolation, cloning and sequence analysis of gene encoding the enolase enzyme from Theileria parva.
FEBS JOURNAL, 2011, 278, 329.
 
Erenler S and Geckil H.
Cloning, isolation and expression of l-asparaginase gene (ansB) in different gram-negative bacteria expressing Vitreoscilla hemoglobin 
 
Celik V, Icen I, Pele P, Munzuroglu O, Geckil H.
Expression of gene encoding Theileria parva enolase in Escherichia coli JM103 strain 
 
Ates B, Gencer S, Erenler SO, Uckun M, Ozer U, Yilmaz I, and Geckil H.
Production of L-asparaginase, a chemotherapeutic enzyme, in bacteria expressing Vitreoscilla haemoglobin.
FEBS JOURNAL, (2006); 273: 139-139.
 
Kahraman H, Gencer S, Geckil H.
Effect of Vitreoscillaon L-lysine alpha-oxidase, a chemotherapeutic enzyme, from Pseudomonas aeruginosa.
FEBS JOURNAL, (2006); 273: 139-140.
 
PUBLICATIONS in TURKISH LANGUAGE
A-01: Aydin S, Geckil H, Caylak E and Kilic N (2004). Mikroorganizmalarin kanser tedavisinde kullanimi.
Firat Medical Journal, 9(2): 30-34.
 
A-02: Kahraman H and Geckil H* (2005). Benzoik Asitin Vitreoscilla hemoglobin geni aktarılmış Pseudomonas aeruginosa tarafından yıkımı.
Fen ve Muhendislik Bilimleri Dergisi, Firat Universitesi, 17(2); 342-348.
 
A-03: Geckil H (2005). "Iki Emekli Bilim Adaminin Hikayesi: Genetige Karsi Biyokimya".
 
A-04: Geckil H (2006). "Molekuler Yasam Bilimlerinde Ph.D. Derecesi Icin Standartlar" (Uluslararasi Biyokimya ve Molekuler Biyoloji Birliği (IUBMB)'nin "Standarts for the Ph.D. Degree in the Molecular Biosciences" isimli orijinal calismasindan yapilmiş Turkce tercume). 
This copyright free study has been published or publicized in: 
A-05: Hikmet Geçkil. Genomlarla Eğlence: Mikoçiğner DNA Bulmacası (A translation of the original article: "Fun with genomes: the Mycomuncher DNA Puzzle")
Science in School, 2007: 1(5); 28-31.
A-06: Hikmet Geçkil. Gözler Ufukta, ayaklar yerde: Tim Hunt'la söyleşi (A translation of the original article "Eyes on the horizon, feet on the ground: interview with Tim Hunt") 
Science in School, 2007: 1(6); 9-13.
A-07: Hikmet Geçkil. Romalılara ait yollar, tren istasyonları ve kontrolörler: RNA araştırmalarında son buluşlar (A translation of the original article "Of Roman roads, train yards and inspectors: recent discoveries in RNA research
Science in School, 2007: 1(6); 20-24. 
A-08: Aslı Giray Kurt ve Hikmet Geçkil. Proteini kristallere büyütme (A translation of the original article "Growing crystals from proteins") 
Science in School, 2009: 11; 30-36. 

A-09: Emel Aytan ve Hikmet Geçkil. Folik asit: öğrenciler neden bu konuyu bilmeli? (A translation of the original article "Folic acid: why school students need to know about it") 

Science in School, 2009: 13; 59-64. 

A-10: Züleyha Türkoğlu (Almaz) ve Hikmet Geçkil. Okulda nanoteknoloji (A translation of the original article "Nanotechnology in school") 
Science in School, 2008: 10; 70-75.

A-11: Tuğçe Kaymaz ve Hikmet Geçkil. Mikrobik yakıt hücresi: mayadan elektrik üretimi. (A translation of the original article "The microbial fuel cell: electricity from yeast") 

Science in School, 2010: 14; 32-35.

A-12: Canbolat Gürses ve Hikmet Geçkil. Omurilik hasarı: kök hücreler cevaba sahip mi? (A translation of the original article "Spinal cord injury: do stem cells have the answer?").

Science in School, 2013: 26; 38-43.

A-13: Samet Kocabay ve Hikmet Geçkil. Ölümcül proteinler: prionlar. (A translation of the original article "Deadly proteins: prions").

Science in School, 2010, 15: 50-54.

A-14: Tuğçe Kaymaz ve Hikmet Geçkil. Genetik planımızın ortaya çıkarılması. (A translation of the original article "Laying bare our genetic blueprint"). Science in School, 2013, 26; 20-24.
A-15: Selen Çolak ve Hikmet Geçkil. DNA’da Urasil: bir yanlışlık mı ya da sinyal mi? (A translation of the original article "Uracil in DNA: error or signal?").  Science in School, 2011, 18; 27-31.
A-16: Yasemin Gökçek ve Hikmet Geçkil. Kalem ve kağıtla biyoinformatik:  filogenetik ağaç oluşturma. (A translation of the original article "Bioinformatics with pen and paper: building a phylogenetic tree"). Science in School, 2011, 18; 27-31.
 BOOKS CITING OUR WORK
  1. Melatonin: Present and Future (by Pedro Montilla López, Pedro Montilla, Isaac Túnez, 2006, Nova Publishers
  2. Functional Food Ingredients and Nutraceuticals: Processing and Technologies (by John Shi, Jerry W. King, 2006, Taylor & Francis)
  3. Environmental Microbiology: Methods and Protocols. (by John F. T. Spencer, Alicia L. Ragout de Spencer, 2004, Springer)
  4. Dictionary of Nutraceuticals and Functional Foods (by Neason Akivah, Michael Eskin, Tamir Snait, Snait Tamir, 2006, CRC Press)
  5. Aging and Age-related Diseases (by Michal Karasek, 2006, Nova Science Publishers)
  6. Globins and other nitric oxide-reactive proteins (by Robert K. Poole, 2008, Academic Press)
  7. Biosystems: Webster's Facts and Phrases: (by Philip M. Parker, 2008, Icon Group International Inc.)
  8. Mycorrhiza: State of the Art, Genetics and Molecular Biology, Eco-Function (by Ajit Varma, 2008, Springer-Verlag)
  9. Reviews of Environmental Contamination and Toxicology (by David M. Whitacre, 2011, Springer)
  10. Breeding for Fruit Quality (by Matthew A. Jenks, 2011, Wiley-Blackwell)
  11. Advances in Microbial Physiology (by Robert K. Poole, 2011, Academic Press)
  12. Ecoimmunology (by Gregory Demas and Randy Nelson, 2012, Oxford University Press)
  13. Advances in Extracellular Space Research and Application (by Ashton Acton, 2011, Scholarly Editions)
  14. Coherent Raman Scattering Microscopy (Ji-Xin Cheng et al., 2012, CRC Press)
  15. Chitosan-Based Hydrogels: Functions and Applications (Fanglyian Yaoet al., 2012, CRC Press)
  16. Dried Fruits: Phytochemicals and Health Effects (by Cesarettin Alasalvar and Fereidoon Shahidi, 2013, Wiley-Blachwell)
  17. Fruit and Cereal Bioactives: Sources, Chemistry, and Applications (by Özlem Tokuşoğlu and Clifford A Hall III, 2011, CRC Press)
  18. The Know-How of Face Transplantation (by Maria Z. Siemionow, 2011, Springer-Verlag)
  19. Fruit Breeding (by Maria Luisa Badenes, 2012, Springer)
  20. Bioactives in Fruit: Health Benefits and Functional Foods (by Margot Skinner and Denise Hunter, 2013, Wiley-Blackwell)
  21. Bioprocessing Technologies in Biorefinery for Sustainable Production of Fuels, Chemicals and Polymers (by Shang-Tian Yang,Hesham El-Ensashy,Nuttha Thongchul, 2013, Wiley)
  22. Food Analysis by HPLC (by Leo M. L. Nollet and Fidel Toldra, 2013, CRC Press)
  23. Nanomaterials in Tissue Engineering: Fabrication and Applications. 2013, Editör: A K Gaharwar,S Sant,M J Hancock,S A. Woodhead Publishing.
  24. Plant-Based Remediation Processes. 2013, Editör: Dharmendra K. Gupta. Springer Publication.
  25. Surface Modification of Biopolymers. Wiley Publications, 2015, Editör: Vijay Kumar Thakur,Amar Singh Singha.
  26. Standardisation in Cell and Tissue Engineering: Methods and Protocols. Woodhead Publishing, 2013, Editör: V Salih.
  27. Biomimetic Technologies: Principles and Applications. Elsevier, 2015. Editör: Trung Dung Ngo.
  28. Biomaterials Surface Science. Wiley-VCH, 2013. Editör: Andreas Taubert,Joao F. Mano,José Carlos Rodríguez-Cabello.
  29. Toxic Effects of Nanomaterials. Bentham Books, 2012. Editör: Haseeb Ahmad Khan,Ibrahim Abdulwahid Arif.
  30. In-Situ Gelling Polymers: For Biomedical Applications. Springer, 2015, Editör: Xian Jun Loh.
  31. Scaffolds for Tissue Engineering: Biological Design, Materials, and Fabrication. Editör: Claudio Migliaresi,Antonella Motta. Pan Stanford Publishing, 2014.
  32. Handbook of Crystal Growth: Fundamentals. Editör: Tatau Nishinaga. Elsevier, 2014.
  33. Soft Fibrillar Materials: Fabrication and Applications. Editör: Jing Liang Li,Xiang Yang Liu. Wiley-VCH, 2013.
  34. Bioprinting in Regenerative Medicine. Editör: Kursad Turksen. Humana Press, 2015.
PATENTS CITING OUR WORK
  1. US 20120251999 A1 Vitrification systems and methods 
  2. US 9075225 B2 Microscopy imaging 
  3. US 20140087466 A1 Micro blood vessels and tissue ducts
 
"Any intelligent fool can make things bigger, more complex and more violent. It takes a touch of genius and a lot of courage to move in the opposite direction"  Albert Einstein

PROJECTS (as PI)

  • October 1 2007-October 1 2009: Hikmet Geckil, Burhan Ates, Sule Bulut, Aslı Giray Kurt. Production of L-DOPA and dopamine in bacteria expressing Vitreoscilla hemoglobin, A project supported by The Scientific andTechnical Research Council of Turkey, TUBITAK (No: 107T478), Project budget: 100,000 USD plus 1000 USD/monthPhD scholarship for two years.
     
  • 2006-2008: Birol Mutlu, Hikmet Geckil and Sukru Karakus. Some taxonomical studies on genus Erysimum in Turkey. A project supported by The Scientific and Technical Research Council ofTurkey (TBAG 105T126),
    Project budget: 100,000 USD.  
     
  • 30.04.2004-2005: Hikmet Geckil, Suleyman Aydin, Burhan Ates, Sebnem O Erenler, Salih Gencer, Mirac Uckun. Cloning, isolation and expression of L-asparaginase, an antileukemic enzyme, gene (ansB) gene in various Gram-negative bacteria. The State Planning Organization of Turkish Prime Ministry, DPT 2003/K120610 (ARDEB no:104S122), Project budget: 50,000 USD.
  • 2004-2005: The production, chemical characterization and clinical aspects of L-asparaginase of bacterial origin.
    A graduate research project with a 6,000 USD budget supported by the Research Fund Unit of Inonu University, APYB 2004/93.
     
  • 2005-2006: Cloning, expression and isolation of L-asparaginase, an enzyme used in cancer therapy, gene (ansB) in various gram-negative bacteria.
    A graduate research project with a 6,000 USD budget supported by the Research Fund Unit of Inonu University, APYB 2005/25.
     
  • 2003-2004: The use of Vitreoscilla hemoglobin in Enterobacter aerogenes : some industrial applications.
    A project supported by The Scientific and Technical Research Council of Turkey, TUBITAK (TBAG2267(102T197)),
    Project budget: 40,000 USD
  • 2003-2004: The degradation/removal of textile dyes from industrial effluents through the use of biotechnological methods.A collectiveproject supported by The State Planning Organization of Turkish Prime Ministry, (DPT:2003K120610), Project budget: 175,000 USD
     
  • 2002-2003: The industrial use of Pseudomonas aeruginosa engineered with the Vitreoscilla hemoglobin gene. A project supported by the Research Fund Unit of Inonu University, APYB 2002/05, Project budget: 12,000 USD
     
  • 2001: Effect of organic solvents on metabolic and physiological activities of Enterobacter aerogenes engineered with Vitreoscilla hemoglobin gene. A project supported by the Research Fund Unit of Inonu University, APYB 2001/16, Project budget: 5000 USD

RESEARCH PROJECTS REVIEW PANELS

  • Since 2005 serving regularly on either one of TUBITAK review panels:
    • The Basic Sciences Research Group (TBAG)
    • Health Sciences Research Group (SBAG)
    • Public Research Grant Committee (KAMAG)
    • Social Sciences and Humanities Research Group (SOBAG)
    • Technology and Inovation Funding programs Directorate (TEYDEB)
  • Founding Director, Center for Gifted and Talented at Inonu University (2010-2012)
  • Founding Director, Children's University at Inonu University (2010-2012)
  •  Instructure for TÜBİTAK Biology Olympiads (2008-2010)
  • 2012: Nominated by TUBITAK, representing Turkey in "Industrial Biotechnology" section of COMSTECH (Committee on Scientific and Technological Cooperation, İslamabad) under OIC (Organisation of Islamic Cooperation).

RESOURCES

THE GECKIL GENETIC ENGINEERING LABORATORY is located in the west wing of the colossal E-shaped Advanced Research Center (ARC) of Inonu University. The laboratory is fully equipped to support molecular biology and genetic engineering studies. DNA amplification, gene cloning and expression, pathway and metabolic engineering are the type of rearch methodologies being carried out. Some basic tools of the trade in our lab:

  • Apparatus for gel electrophoresis for nucleic acids and protiens, gel imaging system, gel dryers, Southern and Northern blotting
  • PCR: PCR and rt-PCR
  • Chromatographic equipment (e.g., fraction collector) for protein isolation and purification, Western blotting
  • Cell culture room with laminar flow hood, CO2 incubators, inverted microscope
  • Spectrophotometry: UV-Vis spectrophotometers, nanodrop spectrophotometer, UV-Vis transilluminator,  microplate reader
  • Incubators: gyratory and static type, water baths
  • Freezers: refridges (3 –20 oC) and ultralow freezer (–80 oC).
  • Balances: coarse and fine
  • Santrifuges: microfuges, medium and high speed low-temp or ambient-temperature centrifuges
  • Owens: microwave and drying
  • Fermentors (1 liter and 2 liter)
  • Disolved oxygen monitoring system

​Some other ARC instrumentation at our disposal:

  • Multi (3) Fluorescence microplate reader 
  • Transmission electron microscopy (TEM)
  • Scanning electron microscopy (SEM)
  • NMR spectrometry
  • Elemental analysisis apparatus
  • Atomic absorption spectrometry (AAS)
  • Infrared spectrometry
  • High-pressure liquid chromatography (HPLC)
  • Gas chromatography (GC)
  • Gas chromatography/Mass spectrometry (GC/MS)
  • X-ray analysis setting
  • X-ray flourescnet spectrophotometry (XRF)
  • Inductively-coupled plasma system (ICP)
  • Liquid nitrogen genertion system

Databases and Computational Tools   

1. Databases

1.1. Sequences

1.1.1. DDBJ 

1.1.2. EMBL

1.1.3. GenBank

1.1.4. GenBank ftp site

1.1.5. TIGR

1.1.6. Wellcome Trust Sanger Institute

1.2. RNA

1.2.1. Rfam: RNA familiy database

1.2.2. RNA base: Databaseof RNA structures

1.2.3. sRNA: Small RNAdatabase

1.3. Comparative & Phylogenetic

1.3.1. COG: Phylogeneticclassification of proteins

1.3.2. TreeBase: Adatabase of phylogenetic knowledge

1.3.3. XREF: Cross-referencing with model organisms

1.3.4. HomoloGene: Genehomologies across species

1.4. SNPs, Mutations & Variations

1.4.1. dbSNP: Singlenucleotide polymorphism database at NCBI 

1.4.2. HapMap: International HapMap Project

1.4.3. HGVbase : HumanGenome Variation Database

1.5. Microarray & Gene Regulation

1.5.1. GEO: Geneexpression omnibus NCBI

1.5.2. Array Express

1.5.3. SMD: StanfordMicroArray Database 

1.5.4. ChipDB

1.5.5. TRRD: Transcription Regulatory region database

1.5.6. TRANSFAC

1.5.7. JASPA

1.5.8. The Signaling Gateway

1.6. Proteins & Interactions

1.6.1. InterPro

1.6.2. ExPASy Proteomics: Expert ProteinAnalysis System

1.6.3. PRIDE

1.6.4. OPD : OpenProteomics Database

1.6.5. BioGrid

1.6.6. BIND

1.6.7. HPRD

1.6.8. DIP

1.6.9. MiMI

1.7. Reaction Pathways

1.7.1. KEGG: Kyoto Encyclopedia of Genes and Genomes

1.7.2. KEGG ftp site

1.7.3. Biocarta

1.7.4. BioCyc

1.8. Enzyme Databases

1.8.1. BRENDA

1.9. Membrane Transporters

1.9.1. TransportClassification Database

1.9.2. TransportDB

1.10. Glycosylation

1.10.1. Functional Glycomics

1.10.2. Bacterial Carbohydrate Structural Database

1.11. Protein Structure

1.11.1. Protein Data Bank

1.11.2. CATH

1.11.3. Protein Information Resource

1.11.4. Structural Classification of Proteins

1.11.5. Swiss-Prot

1.12. Systems Biology

1.12.1. BiGG Database

1.13. Synthetic Biology

1.13.1. Standard Biological Parts

1.14. Other

1.14.1. Gene Ontology

1.14.2. PubMed

 2. Computational Tools

2.1. Genome Browser

2.1.1. NCBI

2.1.2. Ensembl

2.1.3. UCSC

2.2. Sequences Comparison & Alignment:

2.2.1. NCBI BLAST

2.2.2. WU-BLAST

2.2.3. ClustalW: Multiple sequence alignment

2.2.4. CINEMA: Colour interactive editor formultiple alignments

2.2.5. FASTA

2.3. Promotor & Transcription Regulation

2.3.1. Promotor Scan: Promoter regions based on scoring homologies with putative eukaryoticPol II promoter sequences 

2.3.2. MatInspector: Detection of transciption factor binding sites

2.3.3. TESS: Transcription Element Search System

2.3.4. E. coli DNA-Binding Site

2.4. Microarray & Gene Regulation

2.4.1. MIAME Minimum information about amicroarray experiment

2.4.2. MeV: MultiExperiment Viewer

2.4.3. GenePattern

2.4.4. geWorkBench

2.4.5. Bioconductor

2.4.6. Agilent eArray

2.4.7. DAVID

2.5. Membrane Protein Analysis

2.5.1. DAS: Transmembrane sequence prediction

2.6. Proteomics / Mass Spectrometry

2.6.1. ExPASy Tools

2.7. Protein Structure Visualization

2.7.1. PYMOL

2.8. Metabolism

2.8.1. CellNetAnalyzer / FluxAnalyzer

2.8.2. COBRA Toolbox

2.8.3. FBA

2.9. Pathway

2.9.1. GenMapp

2.9.2. KEGG Tools

2.9.3. GSEA: Gene SetEnrichment Analysis

2.9.4. Extreme Pathway Analysis

2.9.5. PUMA2

2.10. RNA folding

2.10.1. Mfold

2.10.2. Sfold

2.10.3. siRNA SelectionProgram

2.10.4. Vienna

2.11. Oligomer Microarray Design

2.11.1. ArrayOligoSelector

2.11.2. OligoArray 2.0

2.11.3. OligoPicker

2.11.4. OligoWiz 2.0

2.11.5. Picky

2.11.6. ROSO

2.11.7. YODA

2.11.8. GoArrays

2.11.9. OligoSpawn

2.11.10. EC Oligos

2.12. Protein 2-D Structure

2.12.1. Chou-Fasman

2.12.2. NNpredict

2.12.3. PredictProtein

2.12.4. SCRATCH

2.13. Protein 3-D Structure

2.13.1. 3D-PSSM

2.13.2. CPHmodels 2.0

2.13.3. UCLA-DOE

2.13.4. Topology of Protein Structure

2.14. Systems Biology

2.14.1. Cytoscape

2.14.2. Systems Biology Workbench

2.14.3. Ingenuity

2.14.4. GeneGo

2.14.5. Gene Designer

2.14.6. Systems Biology Markup Language

2.14.7. Biowww.net

2.14.8. Tools at Weiznmann Institute