Scientific Approaches

Faculty in the Center for NeuroGenetics and in UF’s neuroscience and genetics community include leading scientists involved in innovative collaborative basic and clinical research in neurogenetic disorders. State-of-the art genomic and proteomic tools and advances in stem cell biology are used in gene discovery efforts and in exploring the biological pathways that may underlie childhood developmental or late-onset disorders of the human nervous system.

Gene discovery

Our research teams are interested in identifying mutations causing novel single-gene disorders. Our strategies combine new high-throughput sequencing technologies with novel gene enrichment tools. These tools allow us to better understand the genetic causes of often ignored or poorly understood neurologic and neuromuscular diseases. We have collected samples from over 450 families affected by known and unknown genetic diseases with a focus on diseases caused by repeat expansion mutations. We have established a network of collaborators across the globe which provides access to other samples when required.

Researcher working in the lab with a dropper device

RNA gain-of-function

Pioneering work in the laboratories of Drs. Swanson, Wang and Ranum have established RNA gain of function as a major mechanism of disease in myotonic dystrophy types 1 and 2 and other repeat expansion disorders. RNA gain of function problems occur when RNAs containing repeated letters of the genetic code accumultate inside cells and sequester, or trap, RNA binding proteins. These proteins in turn are not able to go carry out their normal functions, which results in widespread disruption of the normal RNA processing events which occur cells.  

Repeat Associated Non-ATG (RAN) Translation

Discovered in the laboratory of CNG Director, Dr. Laura Ranum, repeat-associated non-AUG (RAN) translation is the process by which repeat expansion mutations make unexpected proteins without the expected canonical AUG start codon. The process, which circumvents the normal way that proteins are made, producing multiple different proteins. These toxic RAN proteins have been found across numerous expansion diseases, including ALS, and are the focus of several different therapeutic approaches under development by CNG faculty.

In vivo models of human disease

Understanding complex human disorders requires the design, development and utilization of model systems that best mimic the disease feature under study. Model systems can be simple, such as cell lines and organoids derived from patients to complex organisms, such as flies or mice that mimic the disease in multiple organs including behavioral features. CNG researchers generate and use a wide variety of in vivo models to better understand a variety of human diseases and to develop new therapies.

hands pointing at genetic information

Neuronal Function

The brain and central nervous system are the most complex components of the human body and are often affected in repeat expansion diseases.  CNG researchers are interested in understanding the complexity of the human brain, how it develops and how it is affected in human diseases. Key parts of this research are understanding the disease specific effects of individual cellular components, like neurons and glia, and the pathways that develop and are responsible for human memories and thoughts.

Benjamin kidd reviews scans on a computer in the lab

Novel Tool Development and Application

One of the keys to better understanding human disease is the continuous development of new tools and technologies to probe complex molecular and cellular interactions. Our research teams are developing and applying new deep sequencing and imaging technologies, as well as computational and machine learning-based approaches for image analysis and gene discovery. Gene identification is a critical first step that allows researchers to understand the specific causes of disease and to develop ways to block the disease process.