Bioinformatics
Bioinformatics combines computer science and information technology to help us under-
stand biological processes. It can be used in many aspects of biological research including
finding genes, discovering and designing drugs, describing protein structure, and predicting
protein-to-protein interactions.
Current Bioinformatics Projects
Linkage analysis for familial ALS and other inherited disorders.
Linkage analysis is performed using DNA samples from many members of larger fami-
lies with familial ALS (FALS) and other familial neuromuscular disorders in order to
identify the disease-causing genes. The chromosomes are analyzed region by region
and once a likely region is identified, we can use known markers along the chromo-
some to narrow down the area as much as possible. The goal is to narrow the search
down to a manageable number of genes which can then be screened for differences in
affected individuals that are not present in unaffected family members.
Human Genetics
Understanding the genetics of ALS is a major part of our research. We use a variety of
research methods to search for new genes, better understand how known genes function,
investigate the effect of chromosomal rearrangements in ALS, search for genetic influences
on SALS, and more.
Current Projects
SALS Genetic and Environmental Predisposition Study
SALS is a complex disorder, most likely caused by multiple genes interacting with
environmental influences. A specific type of genomic study called an association study
focuses on the influences of suspected genes. Our laboratory is currently involved in
an association study for SALS. These studies use relatives of the person with ALS –
typically siblings and parents – to calculate ratios to determine whether the gene in
question is more or less likely to cause the patient’s ALS. Genes may predispose an
individual to the disease by influencing either the onset or duration. Our laboratory
holds the largest number of samples from families in the world being used for these
association studies so more of these genes are likely to be identified by our team.
Protein Biology
We are also involved in the study of protein biology, which investigates the relationship
between protein structure and protein function. Proteins are the products of our genes, and
perform numerous roles in our bodies – structures, messengers, and signals. Changes in
genes affect the proteins’ structure and thus their ability to perform their normal functions.
High-Throughput Drug Screening
High-throughput screening, or HTS, is a method used in drug discovery. HTS allows
researchers to quickly conduct millions of chemical, genetic, or pharmacological tests. This
helps us to rapidly identify active compounds, antibodies or genes which are involved in a
particular biological process. As a result, these experiments provide starting points for drug
design and for understanding the interaction or role of a particular biochemical process in
biology.
Gene Functions
Genes provide our cells with the instructions they need to function, whether it be brain cells,
skin cells, or bone cells. Although all our cells contain all of our genes, different genes are
active in the different cell types that make up our bodies. Understanding a gene’s function is
an important part of understanding the mechanism of a disease like ALS and could
hopefully lead to the development of effective treatments.
Neuronal Loss and Degradation
The neurodegeneration in ALS leads to progressive weakness, atrophy (muscle wasting),
and often spasticity (excess muscle tone). By seeking to understand the process in which
neurons degrade and are lost, we hope to better understand the mechanism of the disease.
Animal Models
We maintain an ongoing colony of research mice. The mouse with the human gene for
mutant SOD1 was the first ALS laboratory model based on a known cause of the disease,
and remains the most widely used animal model of the disease. These mouse models are
very important for testing potential therapies, since their nervous systems are much larger
and more complex than other animal models, like insects or fish. Recently, rodent models
based on the TDP-43 gene are also available to researchers, and mice with the FUS gene
or the C9ORF72 gene are being developed.