Therapeutic Nanomaterials

Dr. Tekinay and Dr. Güler have recently coauthored a new book by Wiley. The book covers biomedical applications of nanomaterials and is intended to serve as a suitable introduction to materials science and its use in diagnostics and therapeutics for the interested student or medical practitioner.

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Biomaterials

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Neural Regeneration

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Drug Delivery

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Neurodegenerative Disorders

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Stem Cell Research


 

Our laboratory is working on applications of molecular biology and genetics in nanobiotechnology, with emphasis on cell-matrix interactions. We are working in collaboration with several groups from different scientific fields, forming an interdisciplinary working environment for our students and researchers. Our research areas include the elicitation of specific cellular behaviors through extracellular matrix-specific biological signals, in vivo and in vitro characterization of ECM-mimetic nanofiber networks and identification of genetic and molecular bases of neurological disorders. Our research group is highly interdisciplinary and accepts graduate students from Bilkent University’s Neuroscience and Materials Science and Nanotechnology programs.

vesikalık-1Ayse Begum Tekinay
Principal Investigator
Institute of Materials Science and Nanotechnology
Neuroscience Graduate Program
UNAM-National Nanotechnology Research Center
E-mail: atekinay(at)bilkent.edu.tr

Curriculum Vitae

Recruiting PhD and MSc Students

The NBT laboratory is currently accepting graduate students. Candidates with bachelor’s degrees in Molecular Biology, Biology, Chemistry and related fields are welcome to apply.

Postdoctoral Researcher Position Available

We are looking for postdoctoral researchers with a PhD degree or equivalent in Molecular Biology, Biology or related fields. The candidates are required to have good language (English) and interpersonal skills with a passion for good science.

Latest News

Enhanced bone regeneration by glycosaminoglycan mimetic peptide gels

A recent article by research groups of Drs. Ayşe Begüm Tekinay and Mustafa Özgür Güler has shown that injectable bioactive peptide gels can accelerate healing of bone defects. Biomineralization plays a crucial role in bone formation, and mimicking the structural and functional characteristics of native bone ECM components can therefore be used to change the fate of stem cells and induce bone regeneration and mineralization. Glycosaminoglycan (GAG) mimetic peptide nanofibers can interact with several growth factors and enhance the osteogenic activity and mineral deposition of osteoblastic cells, making them ideal materials for the development of biactive scaffolds for tissue engineering.

In this study, they investigated the potential of GAG-mimetic peptide nanofiber gels to promote the osteogenic differentiation of rat mesenchymal stem cells (rMSCs) in vitro and enhance bone regeneration and biomineralization in vivo in a rabbit bone defect model. Histological and micro-computed tomography (Micro-CT) observations of regenerated bone defects showed that the injection of a GAG-mimetic gel supports cortical bone deposition by enhancing the secretion of an inorganic mineral matrix. The volume of the repaired cortical bone was higher in GAG-PA gel injected animals. The overall results indicate that GAG-mimetic peptide nanofibers can be utilized effectively as a new bioactive platform for bone regeneration. This work has been published in the journal Biomaterials Science and selected as a Cover Paper.

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Removing the Mote in God’s Eye: Capillary-Cutting Hydrogels Offer New Hope for Neovascularization Treatment

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Angiogenesis, the formation of new blood vessels, is often desirable in the field of regenerative medicine – but not when a tangle of capillaries are blotting vision by crowding the eyes. This surprisingly common condition, called corneal neovascularization, requires regular treatment by expensive antibodies to stave off the rogue blood vessels, but recent research by Drs. Ayşe Begüm Tekinay and Mustafa Özgür Güler and their doctorate student Berna Şentürk may have discovered a more effective and less expensive alternative.

The groups’ peptide-based approach uses the LPPR sequence, which has previously been shown to inhibit angiogenesis in the eye, to produce a transparent peptide matrix that can be applied directly to the eye. While the non-peptide form of LPPR quickly dilutes out of the ocular orb, the jelly-like peptide matrix is able to remain on site for extended periods of time, continuously blocking the advance of new blood vessels while eliminating the need for renewed treatments.

The application of the LPPR peptide hydrogel also resulted in in vitro blood vessel inhibition rates comparable to the commercial drug bevacizumab (Avastin), while the peptide system was significantly more effective in preventing angiogenesis in an in vivo rat model. Combining efficiency with cost-effectiveness, the peptide model may be developed further to produce “contact lens-like” formulations that are applied once to provide long-term protection against neovascularization.

Dr. Tekinay wins FABED award

UNAM researcher Asst. Prof. Dr. Ayşe Begüm Tekinay received the FABED Eser Tümen Outstanding Young Scientist Award of 2016 in the field of biology. Granted each year to researchers under the age of 40 who have chosen to establish their careers in Turkey, the Eser Tümen awards aim to recognize mid-career scientists who have made major contributions to the country’s academic prowess.

Dr. Tekinay won the Eser Tümen award for her research in the area of understanding the molecular causes of tissue degeneration and developing new generation nanomaterials for tissue repair.

Therapeutic Nanomaterials

Dr. Ayşe Begüm Tekinay and Dr. Mustafa Özgür Güler have recently co-authored a book, Therapeutic Nanomaterials, that details the fundamental aspects of nanotechnology as they pertain to the development of novel materials for applications in medicine. Intended for a general academic audience, the book underlines the importance of both natural and synthetic materials for the treatment of common diseases and injuries, and includes chapters on the design principles of nanomaterials intended for use in the treatment of specialized tissues such as teeth, cartilage and the nervous system.

Peptide delivery system smuggles drugs through blood and into cancer cells

Although it may appear that cells rely almost entirely on proteins to maintain their function, this is far from the case: DNA is not merely a repository of genetic information, nor is RNA a simple vehicle for transforming that information into the all-important proteins. Nucleic acids play direct and important roles in regulating cellular activity, and drugs based on their structure and function are potent agents for the treatment of a wide variety of diseases. Such drugs have one fatal flaw, however: Nucleic acids are not built to last outside the cell, and when administered into the bloodstream, nucleases and other hydrolytic enzymes make quick work of them. Successful application of nucleic acid-based drugs therefore requires a means of protecting them in the blood and delivering them exactly where they may work their magic – and a peptide amphiphile-based system, developed by the groups of Drs. Ayşe Begüm Tekinay and Mustafa Özgür Güler, now provides the capability to do both.

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The delivery vesicle uses a combination of cell-penetrating polyarginine and membrane-targeting KRSR sequences – the highly cationic nature of arginine allows it to pass through the negatively-charged cell membrane, while the proteoglycan-binding KRSR sequence enhances the affinity of the peptide complex to cells. The positive charge of polyarginine is in fact a mixed blessing, as the same mechanism that allows it to penetrate cells also makes it highly cytotoxic – but this toxicity is mitigated when polyarginine is tempered with KRSR-PA, and the combination of both peptide molecules creates a highly effective delivery system that is minimally toxic to non-target cells. When loaded with an antisense oligonucleotide against a breast cancer gene, peptide vesicles were able to decrease the expression of their target with an efficiency comparable to lipofectamine, a cationic liposome system that is commercially provided as a transfection-enhancing agent.

Although breast cancer was the subject of the study, the authors believe that the system can be extended to the treatment of other diseases:  Zahide Didem Mumcuoğlu, the lead author of the study, highlights the clinical failures faced by nucleic acid therapeutics and suggests that “[The present work is] only a small step for the development of effective oligonucleotide-based drugs”.

The research has been published in the journal ACS Molecular Pharmaceutics and can be accessed at the following address:

http://pubs.acs.org/doi/full/10.1021/acs.molpharmaceut.5b00007

UNAM team creates additive-free bone in peptide matrix

Stem cells have long been hailed as a miracle cure for just about any tissue injury, but require a large supporting cast of growth factors, cell metabolites, extracellular matrix elements and physical signals in order to work their magic. While artificial scaffolds can be designed to incorporate these signals, the doping of stem cells is nonetheless a finicky issue – not every material has what it takes to serve as a reservoir for additional growth factors, mimic the structure of the native extracellular matrix and adjust its physical properties to match the tastes of its stem cells, especially since implantable materials are also required to display minimal toxicity and retain an ideal release profile.

While such an ideal material seems unlikely, two research groups from UNAM have recently reported an equally potent alternative: By combining their biological and chemical expertise, the research groups of Drs. Ayşe Begüm Tekinay and Mustafa Özgür Güler have developed a way to simplify the process, producing a peptide nanofiber matrix that requires neither growth factors nor a specific stiffness to induce the differentiation of mesenchymal stem cells into functional bone cells.

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Mesenchymal stem cells possess the widest differentiation capacity among almost any adult stem cell, though their versatility is both a boon and a bane – innate differences between cell populations mean that no two MSCs will be the same, and strong cues for lineage-specific differentiation are required to push the entire population towards a single cell fate. A peptide sequence potent enough to induce osteogenic differentiation without any external support is certainly advantageous for researchers looking into a way of reliably differentiating scaffold-implanted MSCs, and may serve to cut down costs by eliminating the need to use growth factors and other inducers of osteogenesis, which often exceed their scaffolds in price. Alternatively, these materials can be used to further augment the performance of the osteogenic matrix. 

The team is both hopeful of the potential utility of their peptide scaffold, and mindful of the biological implications of their “additive-free” differentiation method. “Since mechanical cues and external osteogenic supplements are known to be an important requirement for osteogenic commitment of stem cells, this study presents a striking example for the ability of a single biological cue to override these requirements.” comments Melike Sever, who led the osteogenic differentiation project. “[This] makes tenascin-C mimetic peptide nanofibers a promising new platform for bone regeneration.”

Their research is published in the journal Biomacromolecules, and supported by the research grant 111M410 of the Scientific and Technological Research Council of Turkey (TUBITAK). It can be accessed from the following hyperlink:

http://pubs.acs.org/doi/full/10.1021/bm501271x

Parkinson Disease and Essential Tremor gene is found

Bilkent University researchers have played a leading role in the identification of a gene that causes Parkinson disease and essential tremor, conditions that afflict many millions of people worldwide. The scientists who conducted the investigation said their study is the first clue that links two common movement disorders and could lead to new treatments.

Under the title “Mitochondrial Serine Protease HTRA2 p.G399S in a Kindred with Essential Tremor and Parkinson Disease,” the study was published the week of November 24 in the Early Edition of the Proceedings of the National Academy of Sciences (USA).

The investigation was a collaborative effort, involving researchers at both Bilkent and the University of Washington, along with clinicians at Hacettepe and Ankara Universities. The team studied a remarkable kin group from Central Anatolia: a six-generation consanguineous Turkish family with both essential tremor and Parkinson disease.

Essential tremor is the most frequent movement disorder of humans and can be associated with substantial disability. The worldwide prevalence is 0.9%, increasing to more than 4% in elderly populations.

Parkinson disease is the second most common neurodegenerative disorder, with a prevalence of 0.3% among the entire population in industrialized countries. The prevalence may rise as high as 1% in those over 60 years of age, and 4% in those over 80. It is estimated that Parkinson disease affects 7 million people globally.

Clinicians have for decades been perplexed by the observation that some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. The Turkish kin group offered scientists a key to elucidating the connection.

After carrying out whole exome sequencing and pedigree analysis in the family, the researchers identified mitochondrial serine protease HTRA2 as the gene likely to be responsible for both conditions. The same mutation had previously been associated with Parkinson characteristics in mouse mutants.

In the Turkish family, inheriting the mutation from one parent (heterozygous) or both parents (homozygous) resulted in essential tremor. However, homozygosity was associated with earlier age, with the onset of tremor occurring in the teens or twenties, and more severe tremor.

Homozygotes, but not heterozygotes, developed Parkinson signs in middle age. The disease is caused by the loss of nerve cells in the brain that produce the chemical dopamine, which helps to control mood and movement.

“We are now studying many more families with essential tremor and Parkinson disease,” said one of the principal authors of the study, Dr. Ayşe Tekinay of the Institute of Materials Science and Nanotechnology at Bilkent.

Geneticists have known for many years that consanguinity, along with multiple children, facilitates gene identification studies that target rare diseases. But it was not explicitly clear until recently that this could also be true for complex and common disease entities such as neurodegeneration, obesity or diabetes.

“I am confident that we will find more genes implicated in complex common diseases through the study of large consanguineous families,” added Prof. Tayfun Özçelik, dean of the Faculty of Science at Bilkent and a member of the Turkish Academy of Sciences.

At present, there is no cure for either essential tremor or Parkinson disease, but medication and brain stimulation can alleviate symptoms in both conditions.

Prof. Mary-Claire King, noted human geneticist, Lasker awardee and a member of the University of Washington Genome Sciences Center, said, “We are very excited about the results of Prof. Tekinay’s research. This is the way forward to understanding the molecular bases of movement disorders and developing new treatment strategies.”

NBT paper receives best manuscript award

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A recent publication by a group of researchers at the Institute of Materials Science and Nanotechnology and UNAM has been selected as one of the “best paper” published in 2013 in the field of atomic layer deposition (ALD). Hakan Ceylan was awarded at the MRS Spring 2014 Meeting in San Francisco, CA, USA.

The selection committee was formed by a group of ALD researchers in Stanford University as well as Research and Development Team of Ultratech/Cambridge Nanotech, the leading manufacturer of ALD systems. As part of the annual ALD User Group Meeting, the 16 best ALD papers (among over 150 papers published published in peer reviewed journals including high impact factor journals such as Nature, Science, and Applied Physics Letters) by Ultratech/Cambridge ALD system users in 2013 were chosen for awards.

A new method for drug delivery in cancer cells

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Asst. Prof. Ayşe Begüm Tekinay, Assoc. Prof. Mustafa Özgür Güler and their students at Bilkent University Institute of Materials Science and Nanotechnology developed a new drug delivery platform for anticancer drugs. The work supported by TÜBA GEBİP and TÜBİTAK was published at the Faraday Discussions, which is a journal of Royal Society of Chemistry. The manuscript was published as an invited article and highlighted in the cover of the issue. The manuscript was also one of the most downloaded 10 articles in the year of 2013 on the web site of the journal.

In this work, peptide molecules were integrated into the liposomal drug delivery platforms to enhance cellular uptake of the anticancer drugs. Liposomes can be used to deliver hydrophilic and hydrophobic drugs due to their structural similarities with cell membrane. Peptides conjugated to a fatty acid can be noncovalently incorporated inside liposomal membrane due to hydrophobic interactions. MCF7 breast cancer cells were treated with anticancer drug containing liposomal systems and enhanced drug activity was observed with peptide integrated liposomes.

NBT group member to meet with Nobel Laureates

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Global Challenges:Opportunities for Nanotechnology, an international nanotechnology workshop organized by the Center for Nanoscience in Munich, the Swiss Nanoscience Institute and ETH Zurich, was recently held on the island of Sen Servolo in Italy. Bilkent was represented at this prestigious event by Hakan Ceylan, a member of NBT group. Among the highlights of the workshop were roundtable discussions with eminent researchers, including Nobel laureates, who pioneered in several important fields.

TÜBA-GEBİP Award of 2012

Dr. Tekinay received the TÜBA-GEBİP Award of 2012 in the field of Materials Science and Nanotechnology. Launched in 2001, the TÜBA-GEBİP award programme aims to foster young, outstanding scientists who are at the stage of establishing their own research programmes in Turkey after finishing their post-doctoral research activities. TÜBA supports these scientists for a period of three years and helps them set up their own research groups at a stage when they are in need for incentives. The selection procedure among GEBIP candidates has very high standards and GEBIP programme is considered as a source of prospective members to the Academy.

L’Oreal Young Women Investigator Award

Dr. Ayse Begüm Tekinay was awarded a L’Oreal Turkey Young Women in Science Fellowship for her studies in regenerative medicine.