PI: Şeref Gül
Circadain rhythm and drug design.
Our research focuses on conducting cutting-edge studies to unravel the intricacies of the mammalian circadian clock mechanism and its connections to chronic diseases, including certain types of cancer, aging, and sleep disorders. By deepening our understanding of these relationships, we aim to identify novel therapeutic targets and develop small molecules with the potential to treat these conditions effectively.
To achieve these ambitious goals, we actively engage in collaborative efforts with renowned research groups both nationally and internationally. These partnerships enable us to integrate diverse expertise, leverage advanced technologies, and drive innovation in addressing the challenges posed by circadian-related disorders.
Seref Gul earned his undergraduate degree in Chemistry from the Faculty of Arts and Sciences at Boğaziçi University. He pursued his master's studies in Chemistry at Boğaziçi University and Michigan State University. In 2019, he completed his Ph.D. in Chemistry and Biological Engineering at Koç University, where he also conducted postdoctoral research until 2021. From 2021 to 2023, he served as an assistant professor at Istanbul University. Since 2023, he has been an associate professor at Bezmialem Vakıf University, where he continues his academic and research endeavors..
- A brief description of the ongoing work
Dr. Gül's research centers on unraveling the molecular mechanisms of the circadian clock in mammals. His team also investigates the relationship between circadian clock gene mutations and various diseases, aiming to identify small molecules with therapeutic potential against these conditions. To achieve this, the Gül group employs an interdisciplinary approach, integrating computer-aided drug discovery tools with in vitro and in vivo molecular biology techniques.
Expertise in Circadian Biology
- Deep knowledge of the molecular mechanisms of the mammalian circadian clock.
- Ability to link circadian clock gene mutations to the development of chronic diseases.
Interdisciplinary Research Approach
- Combines computational drug discovery with experimental molecular biology techniques.
- Bridges computational predictions with biological validation through innovative methodologies.
Therapeutic Development Focus
- Focus on discovering and developing small molecules as potential treatments for circadian-related disorders.
- Targeting diseases such as certain cancers, aging, and sleep-disorder conditions.
Collaboration and Innovation
- Engages in active national and international collaborations to enhance research capabilities.
- Embraces multidisciplinary approaches to foster innovation and impactful discoveries.
As a team, we are committed to pioneering research to unravel the complexities of the mammalian circadian clock and its profound influence on chronic diseases, including certain types of cancer, aging, and sleep disorders. Our vision is to transform this understanding into actionable insights, identifying novel drug targets and developing small molecules with the potential to revolutionize the treatment of these conditions.
We strive to foster a collaborative and innovative research environment by partnering with leading national and international research groups. Through these partnerships, we aim to integrate diverse expertise, adopt cutting-edge technologies, and drive impactful discoveries that advance both science and medicine. Together, we aspire to push the boundaries of knowledge and deliver solutions that improve health and well-being worldwide.
Proven Research Expertise
- High-impact publications demonstrating significant contributions to circadian biology and drug development.
Technical Proficiency
- Mastery of computational tools for drug discovery, as well as in vitro and in vivo molecular biology techniques.
Track Record of Translational Research
- Successful integration of basic science with applied therapeutic development.
Effective Collaboration
- Strong connections with national and international research groups, enhancing access to diverse expertise and cutting-edge resources.
Innovative Vision
- Clear research goals focused on translating fundamental findings into real-world therapeutic applications.
Field of expertise
Circadian clock, Drug design
Affiliations
Bezmialem Vakif University Life Science and Biotechnology Institute, Biotechnology Division
List of publications
Discovering Lassa virus nucleoprotein inhibitors via in silico drug repositioning approach
Gul S., Simsek H. Journal of Biomolecular Structure and Dynamics, 2024
TW68, cryptochromes stabilizer, regulates fasting blood glucose levels in diabetic ob/ob and high fat-diet-induced obese mice
Surme S., Ergun C., Gul Ş., AKYEL Y. K., Gul Z. M., Ozcan O., et al. Biochemical Pharmacology , cilt.218, 2023 (SCI-Expanded) Functional characterization of the CRY2 circadian clock component variant p.Ser420Phe revealed a new degradation pathway for CRY2.
Parlak G. C., Baris I., Gul Ş., Kavakli I. H. The Journal of biological chemistry , cilt.299, sa.12, ss.105451, 2023 (SCI-Expanded) Dynamic regulation of the serine loop by distant mutations reveals allostery in cryptochrome1
Ozcan O., Gul Ş., Kavakli I. H. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS , 2023 (SCI-Expanded) Synthesis of Novel Hybrid Lonidamine-Coumarin Derivatives and Their Anticancer Activities
Ipek O. S., SUCU B. O., Gul Ş., YOLAÇAN Ç., GÜZEL M. JOURNAL OF MOLECULAR STRUCTURE , cilt.1281, 2023 (SCI-Expanded) Diurnal Changes in Capecitabine Clock-Controlled Metabolism Enzymes Are Responsible for Its Pharmacokinetics in Male Mice.
Akyel Y. K., Öztürk Civelek D., Ozturk Seyhan N., Gul Ş., Gazioglu I., Pala Kara Z., et al.
Journal of biological rhythms , cilt.38, sa.2, ss.171-184, 2023 (SCI-Expanded) Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice
Gul Ş., Akyel Y. K., Gul Z. M., Isin S., Ozcan O., Korkmaz T., et al. Nature Communications , cilt.13, sa.1, 2022 (SCI-Expanded) Analysis of ACE2 and TMPRSS2 coding variants as a risk factor for SARS-CoV-2 from 946 whole-exome sequencing data in the Turkish population
DUMAN N., Tuncel G., BİŞGİN A., TUĞ BOZDOĞAN S., ÖZEMRİ SAĞ Ş., Gul Ş., et al. JOURNAL OF MEDICAL VIROLOGY , cilt.94, sa.11, ss.5225-5243, 2022 (SCI-Expanded) The secondary pocket of cryptochrome 2 is important for the regulation of its stability and localization
Parlak G. C., Camur B. B., Gul Ş., Ozcan O., Baris I., Kavakli I. H. Journal of Biological Chemistry , cilt.298, sa.9, 2022 (SCI-Expanded) Proteome analysis of the circadian clock protein PERIOD2
Gul H., Selvi S., Yilmaz F., Ozcelik G., Olfaz-Aslan S., Yazan S., et al. Proteins: Structure, Function and Bioinformatics , cilt.90, sa.6, ss.1315-1330, 2022 (SCI-Expanded) In Silico Analysis of a de Novo OTC Variant as a Cause of Ornithine Transcarbamylase Deficiency
Ozdemir Y., Cag M., Gul Ş., Yüksel Z., Ergoren M. C. Applied Immunohistochemistry and Molecular Morphology , cilt.30, sa.2, ss.153-156, 2022 (SCI-Expanded) Structure-based design and classifications of small molecules regulating the circadian rhythm period
Gul Ş., Rahim F., Isin S., Yilmaz F., Ozturk N., Turkay M., et al. Scientific Reports , cilt.11, sa.1, 2021 (SCI-Expanded) Identification of a Novel de Novo COMP Gene Variant as a Likely Cause of Pseudoachondroplasia
Tuncel G., Akcan N., Gul Ş., Sag S. O., Bundak R., Mocan G., et al. Applied Immunohistochemistry and Molecular Morphology , cilt.29, sa.7, ss.546-550, 2021 (SCI-Expanded) In silico drug repositioning against human nrp1 to block sars-cov-2 host entry
Gül Ş.
Turkish Journal of Biology , cilt.45, sa.Special Issue 1, ss.442-458, 2021 (SCI-Expanded) In silico identification of widely used and well-tolerated drugs as potential SARS-CoV-2 3C-like protease and viral RNA-dependent RNA polymerase inhibitors for direct use in clinical trials
Gul Ş., Ozcan O., Asar S., OKYAR A., Barıs I., Kavakli I. H. Journal of Biomolecular Structure and Dynamics , cilt.39, sa.17, ss.6772-6791, 2021 (SCI-Expanded) Transcriptome analysis of the circadian clock gene BMAL1 deletion with opposite carcinogenic effects
Emisoglu-Kulahli H., Gul Ş., MORGİL GERÇEK H., Ozcan O., Aygenli F., Selvi S., et al. Functional and Integrative Genomics , cilt.21, sa.1, ss.1-16, 2021 (SCI-Expanded) The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm
Gul Ş., Aydin C., Ozcan O., Gurkan B., Surme S., Baris I., et al. Journal of Biological Chemistry , cilt.295, sa.50, ss.17187-17199, 2020 (SCI-Expanded) Unique combination and in silico modeling of biallelic POLR3A variants as a cause of Wiedemann–Rautenstrauch syndrome
TEMEL Ş. G., Ergoren M. C., Manara E., Paolacci S., Tuncel G., Gul Ş., et al. European Journal of Human Genetics , cilt.28, sa.12, ss.1675-1680, 2020 (SCI-Expanded) Human CRY1 variants associate with attention deficit/hyperactivity disorder.
Emre Onat O. E., Ece Kars M., Gül Ş., Bilguvar K., Wu Y., Özhan A., et al. The Journal of clinical investigation , cilt.130, sa.7, ss.3885-3900, 2020 (SCI-Expanded) A CLOCK-binding small molecule disrupts the interaction between CLOCK and BMAL1 and enhances circadian rhythm amplitude
Doruk Y. U., Yarparvar D., Akyel Y. K., Gul Ş., Taskin A. C., Yilmaz F., et al. Journal of Biological Chemistry , cilt.295, sa.11, ss.3518-3531, 2020 (SCI-Expanded) Identification and Characterization of a New Class of (6-4) Photolyase from Vibrio cholerae
Dikbas U. M., Tardu M., Canturk A., Gul Ş., Ozcelik G., Baris I., et al. Biochemistry , cilt.58, sa.43, ss.4352-4360, 2019 (SCI-Expanded) Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation
Odabasi E., Gul Ş., Kavakli I. H., Firat-Karalar E. N. EMBO Reports , cilt.20, sa.6, 2019 (SCI-Expanded) DNA repair by photolyases.
Kavakli I. H., Ozturk N., Gul Ş. Advances in protein chemistry and structural biology , cilt.115, ss.1-19, 2019 (SCI-Expanded) The Photolyase/Cryptochrome Family of Proteins as DNA Repair Enzymes and Transcriptional Repressors
Kavakli I. H., Baris I., Tardu M., Gül Ş., Öner H., Çal S., et al. Photochemistry and Photobiology , cilt.93, sa.1, ss.93-103, 2017 (SCI-Expanded) Glu-370 in the large subunit influences the substrate binding, allosteric, and heat stability properties of potato ADP-glucose pyrophosphorylase
Seferoglu A. B., Gul Ş., Dikbas U. M., Baris I., Koper K., ÇALIŞKAN M., et al. Plant Science , cilt.252, ss.125-132, 2016 (SCI-Expanded) Conformational sampling of peptides in the presence of protein crowders from AA/CG-multiscale simulations
Predeus A. V., Gul Ş., Gopal S. M., Feig M. Journal of Physical Chemistry B , cilt.116, sa.29, ss.8610-8620, 2012 (SCI-Expanded) Computational study of factors controlling the boat and chair transition states of ireland-claisen rearrangements
Gül Ş., Schoenebeck F., Aviyente V., Houk K. Journal of Organic Chemistry , cilt.75, sa.6, ss.2115-2118, 2010 (SCI-Expanded)
Gül Lab Projects
- Şeref Gül Ilaç Yeniden Konumlandırma Metoduyla Biyogüvenli SARS-CoV-2 Replikonu Kullanılarak SARS-CoV-2 Inhibitörü Bulunması Completed
- Şeref Gül Sirkadiyen saatin pankreas kanserindeki işleyişini anlamak ve pankreas kanserinde CRY proteinleri rolünün incelenmesi Ongoing
- Şeref Gül p53 Nakavt Hücrelerde Apoptozu Artıran CRY1 Kararsızlaştırıcı Küçük Molekül M47'nin Fragman Bazlı Optimizasyon Yöntemi İle Etkinliğinin Artırılması Ongoing
- Şeref Gül P53 Fonksiyon Kazanımı Mutasyonlarına Sahip Farklı Pankreas Kanseri Hücre Hatlarında Sirkadiyen Ritmin Araştırılması Ongoing
Ongoing Grants
| 2024-2026 |
| Title: Understanding the Activity Mechanism of Small Molecule JET1 Regulating the Circadian Rhythm Amplitude and Its Effects on Jet-Lag |
| Status: Awarded |
| Identification number: 35578 |
| Sponsor: Health Institutes of Türkiye (TUSEB Group-B) |
| Total direct cost: TLR 2.499.750,00 |
| Principal Investigator: Şeref Gül |
| Partners: Koc University, Türkiye |
| Role: Principal Investigator |
| 2024-2026 |
| Title: Improving the Efficacy of CRY1 Destabilizer Small Molecule M47 that Enhances Apoptosis in p53 Knockout Cells by Fragment Based Optimization Method |
| Status: Awarded |
| Identification number: 35805 |
| Sponsor: Health Institutes of Türkiye (TUSEB Group-B) |
| Total direct cost: TLR 2.499.315,00 |
| Principal Investigator: Şeref Gül |
| Partners: Koc University, Türkiye |
| Role: Principal Investigator |
| 2024-2026 |
| Title: Discovery of genes linked to sleep disorders, their molecular characterization, and investigation of their roles in disease pathogenesis |
| Status: Awarded |
| Identification number: 40691 |
| Sponsor: Health Institutes of Türkiye (TUSEB Group-B) |
| Total direct cost: TLR 2.633.370 |
| Principal Investigator: Onur Emre Onat |
| Partners: - |
| Role: Researcher |
| 2023-2024 |
| Title: Identification of Proteins that Interact with Biotinylated-Terpinolene in MCF7 Cells and Modeling of These Interactions |
| Status: Awarded |
| Identification number: 31728 |
| Sponsor: Health Institutes of Türkiye (TUSEB Group-A) |
| Total direct cost: TLR 124.979,70 |
| Principal Investigator: Cenk Kig |
| Partners: Istanbul University, Türkiye |
| Role: Researcher |
| 2024-2026 |
| Title: Examining the Circadian Rhythm in Different Pancreatic Cancer Cell Lines with Gain-of-Function p53 Mutations |
| Status: Awarded |
| Identification number: BAP-2024-0624 |
| Sponsor: BAP |
| Total direct cost: TLR 50.000,00 |
| Principal Investigator: Şeref Gül |
| Partners: - |
| Role: Principal Investigator |
| 2024-2026 |
| Title: Examining the Effect of Cryptochrome Deletion in Various Pancreatic Cancer Cell Lines with Gain-of-Function p53 Mutations |
| Status: Awarded |
| Identification number: 123N147 |
| Sponsor: TUBITAK |
| Total direct cost: TLR 800.000,00 |
| Principal Investigator: Halil Kavaklı |
| Partners: Munih Technical University |
| Role: Researcher |
- Completed grants/projects
Completed Projects:
| Discovery of a SARS-CoV-2 Inhibitor Using Biosafe SARS-CoV-2 Replicon via Drug Repurposing Method |
| Determining the Effect of Pathogenic BMAL1 SNPs on the Circadian Clock Mechanism |
| Pharmacokinetics of CLK8 Compound, which Regulates the Function of CLOCK Protein, in Mice |
| Analyzing the in vivo effects of CLK8 Molecule |
| Drug repurposing against Lassa virus proteins by using in silico methods (Master Thesis) |
| Drug design against SARS-CoV-2 virus via drug repurposing by using in vitro methods (Master Thesis) |
Completed Grants:
| 2022-2024 |
| Title: Drug design against SARS-CoV-2 virus via drug repurposing by using in vitro methods |
| Status: Completed |
| Identification number: FYL-2023-40043 |
| Sponsor: IU BAP |
| Total direct cost: TLR 80.000 |
| Principal Investigator: Mahmut Çalışkan |
| Partners: Istanbul University, Türkiye |
| Role: Researcher |
| 2022-2024 |
| Title: Discovery of a SARS-CoV-2 Inhibitor Using Biosafe SARS-CoV-2 Replicon via Drug Repurposing Method |
| Status: Completed |
| Identification number: 221Z267 |
| Sponsor: TUBITAK - 3501 |
| Total direct cost: TLR 544.638 |
| Principal Investigator: Şeref Gül |
| Partners: - |
| Role: Principal Investigator |
- Achievements as a lab/team.
- Your approach as a PI for aspiring scientists and students to build a strong and trained scientific community in Turkey. How you perceive that BILSAB as an institute is helping you in doing so.(What can/ are you offer via BILSAB).
Mentorship and Skill Development
- Provide personalized mentorship to guide students and early-career scientists in developing both technical and analytical skills.
- Offer training in cutting-edge methodologies, including computer-aided drug discovery, molecular biology techniques, and circadian biology research.
Interdisciplinary Learning
- Encourage cross-disciplinary approaches by integrating computational and experimental research methods.
- Expose trainees to collaborative projects involving molecular biology, pharmacology, and systems biology.
Hands-On Research Experience
- Involve students in real-world research projects that contribute to the understanding of circadian mechanisms and therapeutic development.
- Promote active participation in experimental design, data analysis, and manuscript preparation.
Fostering Innovation
- Inspire students to think creatively and pursue novel ideas within the broader scope of circadian biology and drug development.
- Support independent research initiatives that align with the group's goals.
Global Collaboration Opportunities
- Facilitate connections with leading national and international research groups, allowing students to gain diverse perspectives and experiences.
- Provide opportunities for collaborative publications and conference presentations.
Commitment to Professional Growth
- Offer seminars, and journal clubs to enhance scientific communication and critical thinking skills.
- Prepare aspiring scientists for careers in academia, industry, or beyond by providing career guidance and networking opportunities.
Inclusive and Supportive Environment
- Foster a collaborative and inclusive culture that values diverse perspectives and ideas.
- Encourage teamwork, open communication, and mutual respect among all members of the group.
Focus on Impactful Research
- Instill a sense of purpose by emphasizing the translational potential of research in addressing real-world challenges, such as chronic diseases and circadian-related disorders.
Role of BILSAB
BILSAB plays a pivotal role in supporting our research group's goals by providing an environment rich in resources, collaboration, and motivation. The institute offers state-of-the-art facilities, including advanced molecular biology labs, in vivo mouse facilities, and a cluster computer center, which are essential for our research on circadian rhythms and small molecule development. Its interdisciplinary approach fosters collaboration, enabling our team to engage with experts from various fields and sparking innovative ideas. Additionally, BILSAB's supportive and tranquil atmosphere, coupled with weekly seminars and social events, ensures that we remain motivated and productive. BILSAB is instrumental in helping us achieve our research objectives and push the boundaries of scientific discovery.
About the team:
Gül LAB team aims to achieve the highest efficiency and success by keeping cooperation and communication among the team at the highest level.
- Number of the team members/students in lab
1 person of PhD student, 5 people of Master's student, 5 people of undergraduate student (volunteer interns)
Selahattin Aydoğan: Technician / Master's Student
Betül Oruçoğlu: Research Assistant / PhD Student
Ayşenur Çakmak: Master's Student
Hursima İzgiş: Master's Student
Mustafa Sami Özaydın: Graduate Student
Buse Avcı: Research Assistant / Master's Student
- Introduction of the team members.
Selahattin Aydoğan
Undergraduate Education: 2022 – Istanbul University – Molecular Biology and Genetics
Master's Education: Present – Istanbul University – Biotechnology
Betül Oruçoğlu
Undergraduate Education: 2021 – Marmara University – Bioengineering
Master's Education: 2024 – Istanbul University – Biotechnology
PhD Education: Present – Bezmialem Vakif University – Biotechnology
Ayşenur Çakmak
Undergraduate Education: 2024 – Üsküdar University – Molecular Biology and Genetics
Master's Education: Present – Bezmialem Vakif University – Biotechnology
Hursima İzgiş
Undergraduate Education: 2021 – Yıldız Technical University – Molecular Biology and Genetics
Master's Education: Present – Istanbul University – Biotechnology
Mustafa Sami Özaydın
Undergraduate Education: 2024 – Istanbul Technical University – Molecular Biology and Genetics
Buse Avcı
Undergraduate Education: 2022 – Istanbul University – Molecular Biology and Genetics
Master's Education: Present – Istanbul University – Molecular Biotechnology and Genetics
Selahattin Aydoğan
BILSAB is an ideal institute for those dedicated to research. It offers all the necessary facilities in one place, eliminating the need to look elsewhere. Additionally, its location provides a calming and comfortable environment.
Betül Oruçoğlu
BILSAB offers researchers a modern infrastructure with laboratories equipped with cutting-edge technology. This dynamic structure, where researchers from different disciplines come together, offers a collaborative atmosphere that encourages interdisciplinary projects and allows innovative ideas to emerge. In addition to the facilities needed for research, BILSAB prioritizes motivation, which is one of the biggest supporters of scientific productivity. In addition to a peaceful, friendly and supportive working environment, there are social events that inspire researchers, a large and spacious garden and recreation area for a pleasant break.
Ayşenur Çakmak: “BILSAB has interdisciplinary proffessors who are experts in their fields. In addition to its state-of-the-art laboratories for both wet and dry labs, it provides all kinds of opportunities for the institute members to be productive with its BILSAB seminars, motivational events and a garden suitable for taking breaks with the unique air of Beykoz."
Hursima İzgiş : “BILSAB is an institute with state-of-the-art laboratories and a great location. It is also located in the Beykoz district, which has a wonderful nature, which adds to its advantage."
Mustafa Sami Özaydın: “BILSAB not only offers well-equipped laboratory facilities but also provides numerous opportunities to easily communicate and consult with the professors at the institute. Additionally, its spacious and serene garden provides a relaxing environment, allowing us to unwind and recharge during breaks between experiments."
Buse Avcı:"BILSAB is researcher and student-friendly, offering research opportunities, expert professors who guide researchers at every step, and a welcoming work environment."
Handan Şimşek – Istanbul University Biotechnology PhD Program.