Despite decades of research, there are still only limited treatments and no cures available for most disorders of the brain, from Parkinson’s disease to Schizophrenia. These diseases represent some of the most challenging areas in drug discovery, and together affect >5% of individuals in G7 countries. Considering the enormous economic burden of these diseases and the absence of efficacious treatments, it is imperative that new therapies are developed. For this to happen, we need to consider more physiological models that most closely resemble neurons within the human brain, and new technologies and methodologies to interrogate neurons in an unprecedented manner to previous approaches. Over the past decade, we have seen significant advances in this area, with induced pluripotent stem cells (iPSCs) providing us the means to readily generate and grow many of the cell types found within the brain on a dish for both research and drug discovery purposes.
Moving beyond 2D cultures, 3D neuronal organoids can now be generated from these patient-derived iPSCs and supporting these efforts is CRISPR genome editing, which emerged at the same time. This provides researchers with the tools to edit cells at the level of one base pair, to add new reporters and to develop novel genome-wide screening paradigms for target identification studies. These technologies have also improved the relevance of drug discovery campaigns as well as allowed comparison of a phenotypic result resulting from small molecule treatment with that elicited by genetic editing. Taken together, we have never been better positioned than we are at this moment to grow and test neurons from all angles, with the ultimate goal of better understanding these neurons and using them to improve our development of therapies that will someday enter the clinic.
With this in mind, this Research Topic is aimed at exploring new tools and technologies for studying neurons in the dish. We aim to broaden our current understanding on new emerging tools and technologies to complement iPSCs, organoids, and CRISPR genome editing, that can help us study and test new ideas with neuronal cultures. Chemical tools, including heterobifunctional, chemical probes, and small molecules are an essential piece of this emerging field.
In this Reserach Topic we welcome Original Research articles and Review submissions focused on (but not limited to):
- New iPSC and CRISPR technologies for studying neuronal function and activity
- Novel genetic approaches to identify new genes or targets associated with a given CNS disorder
- Advanced imaging and electrophysiological approaches for studying neurons in both 2D and 3D cultures
- Development of next-generation biomaterials and microfluidic systems that can be used to grow and manipulate neurons in unconventional manners
- Exploration of single-cell phenotyping techniques of neuronal cultures
- Novel software and analysis pipelines for better studying novel data sets emerging from neurons
- Testing of new approaches, methodologies, and techniques for developing novel CNS-focused therapies and small molecules
- Study of rare neurodegenerative diseases using neuronal models
- Chemogenomic strategies in neuroscience drug discovery
- Novel small molecule approaches to target disease-causing pathways in the brain
- Identification of and strategies to modulate previously unexplored protein targets that are proposed to propagate CNS disorders
- New directions in neuroscience drug discovery that rely on the use of iPSCs
- Use of iPSCs to model and improve brain penetration of drug candidates
Despite decades of research, there are still only limited treatments and no cures available for most disorders of the brain, from Parkinson’s disease to Schizophrenia. These diseases represent some of the most challenging areas in drug discovery, and together affect >5% of individuals in G7 countries. Considering the enormous economic burden of these diseases and the absence of efficacious treatments, it is imperative that new therapies are developed. For this to happen, we need to consider more physiological models that most closely resemble neurons within the human brain, and new technologies and methodologies to interrogate neurons in an unprecedented manner to previous approaches. Over the past decade, we have seen significant advances in this area, with induced pluripotent stem cells (iPSCs) providing us the means to readily generate and grow many of the cell types found within the brain on a dish for both research and drug discovery purposes.
Moving beyond 2D cultures, 3D neuronal organoids can now be generated from these patient-derived iPSCs and supporting these efforts is CRISPR genome editing, which emerged at the same time. This provides researchers with the tools to edit cells at the level of one base pair, to add new reporters and to develop novel genome-wide screening paradigms for target identification studies. These technologies have also improved the relevance of drug discovery campaigns as well as allowed comparison of a phenotypic result resulting from small molecule treatment with that elicited by genetic editing. Taken together, we have never been better positioned than we are at this moment to grow and test neurons from all angles, with the ultimate goal of better understanding these neurons and using them to improve our development of therapies that will someday enter the clinic.
With this in mind, this Research Topic is aimed at exploring new tools and technologies for studying neurons in the dish. We aim to broaden our current understanding on new emerging tools and technologies to complement iPSCs, organoids, and CRISPR genome editing, that can help us study and test new ideas with neuronal cultures. Chemical tools, including heterobifunctional, chemical probes, and small molecules are an essential piece of this emerging field.
In this Reserach Topic we welcome Original Research articles and Review submissions focused on (but not limited to):
- New iPSC and CRISPR technologies for studying neuronal function and activity
- Novel genetic approaches to identify new genes or targets associated with a given CNS disorder
- Advanced imaging and electrophysiological approaches for studying neurons in both 2D and 3D cultures
- Development of next-generation biomaterials and microfluidic systems that can be used to grow and manipulate neurons in unconventional manners
- Exploration of single-cell phenotyping techniques of neuronal cultures
- Novel software and analysis pipelines for better studying novel data sets emerging from neurons
- Testing of new approaches, methodologies, and techniques for developing novel CNS-focused therapies and small molecules
- Study of rare neurodegenerative diseases using neuronal models
- Chemogenomic strategies in neuroscience drug discovery
- Novel small molecule approaches to target disease-causing pathways in the brain
- Identification of and strategies to modulate previously unexplored protein targets that are proposed to propagate CNS disorders
- New directions in neuroscience drug discovery that rely on the use of iPSCs
- Use of iPSCs to model and improve brain penetration of drug candidates
