MSE Special Seminar: Dr. Halil Tekin, Engineering biomaterial-templated genetically tractable 3D models of the human brain

Abstract

Understanding of neurological diseases requires tractable systems in which to interrogate the genetic underpinnings of these complex diseases. Previously developed three-dimensional (3D) neural tissue systems have not enabled genetic studies and lacked neuronal and astrocytic cells rapidly derived from human embryonic stem cells (hESCs). It is also not well understood how transcriptome profiles of these tissues are impacted by encapsulating materials and relate to that of the human brain, limiting their application as disease models. In this talk, I will present the development of tunable 3D human neural tissues using cells rapidly derived from hESCs and biomaterials. Gene profiling of these tissues displayed enriched signatures of neurological processes compared to conventional two-dimensional cultures, with further transcriptomic complexity accomplished by co-culturing neurons with astrocytes in 3D composite hydrogels of basement membrane matrix and alginate. By comparing the transcriptomic profiles of neuronal cells in 3D tissues to the human brain developmental transcriptome, we demonstrated that modifying the degree of crosslinking of composite hydrogels alters the correlation to subregions of human fetal brain at specific stages of development. We further extended our method to form neural tissues better representing cell composition in the human brain by deriving astrocytic cells directly from hESCs and combining these astrocytic cells with neuronal cells in a 3D matrix. Using single-cell sequencing, we found that our system recapitulates transcriptional patterns of cell types in the human brain. Finally, we demonstrated that this 3D tissue system can be combined with gene editing and delivery tools to allow large-scale interrogation of neurological disease genes. Our study interfacing biomaterials engineering and neuroscience will further aid the development of more-effective models of the human brain at health or disease state.

Bio

Dr. Halil Tekin completed his Ph.D. at MIT in the laboratories of Dr. Ali Khademhosseini and Dr. Robert Langer. He then performed his postdoctoral research at the Broad Institute of MIT and Harvard in the laboratory of Dr. Feng Zhang. During his graduate studies, he received MIT’s Outstanding Undergraduate Research Mentor Award, Bioanalysis Highly Commended Young Investigator Award, JALA Ten Award, and the Materials Research Society Best Oral Presentation Award. Prior to MIT, Dr. Tekin received his B.S. and M.S. degrees from Istanbul Technical University (ITU) with the first rank among Control Engineering program graduates and Electrical Engineering department graduates. During his time at ITU, he is the recipient of Siemens Excellence Award, ITU Rectorate Award, and Ord. Prof. Bedri Karafakioglu Award. Dr. Tekin’s research focuses on modelling and understanding brain diseases towards developing regenerative therapeutics by interfacing materials science and engineering, neuroscience, stem cell biology, and genomic technologies.