Integrating Metabolomics and Proteomics

Scientists Dig Deeper into Aging through Buck’s
New Center for Integrative Metabolomics and Proteomics

Think of it as high tech forensics for solving the mystery of aging – with the goal of developing treatments to slow a process that underlies the majority of chronic diseases.

Gibson and RamanthanThe state-of-the-art technology platform is housed in the new Center for Integrative Metabolomics and Proteomics of Aging, a new initiative at the Buck Institute.  Led by professors Brad Gibson and Arvind Ramanathan, this center allows scientists to delve deeper into the molecular underpinnings of aging and age-related diseases by identifying key proteins and metabolites in a highly coordinated approach.

Many people are familiar with the idea of genomics, or the study of genes encoded in the human genome and their function. Through a process called DNA sequencing, a person’s entire genome can be mapped and the order of DNA nucleotides in each gene determined. This technology allows for the identification of genetic mutations, or differences in the normal DNA sequence of a gene, which alter protein function and can cause disease in humans. Genomics has had a huge impact on drug discovery and therapeutic development. Scientists can screen libraries of drug compounds to identify compounds that target genes whose functions are altered in specific disease states and correct or replace those functions.

Going beyond genomics

But genomics isn’t enough to tell the whole story. While genes provide the blueprint for cell activity, there can be a lot of variability in how genes are expressed and how downstream molecular players interact with each other or alter the structures of proteins. To obtain a deeper level of understanding of these processes, Gibson and Ramanathan’s new center integrates metabolomics and proteomics technologies. Metabolomics is the study of metabolites or small molecules generated during specific cellular processes. As its name suggests, metabolomics generates molecular profiles of a cell’s metabolism and physiology. Proteomics is the study of proteins including their functions, cellular localizations, and structures. The proteome is a landscape of all proteins within a cell that can change over time as cells age or are exposed to stressful environments. Gibson and Ramanathan are taking a unique systems approach to the biology of aging, whereby the analysis of protein expression and protein-protein interactions are done in tandem with the mapping of metabolic pathways and the rate of turnover of molecules within the pathway.

The 'Omics

A unique combination of expertise

In their new Center for Integrated Metabolomics and Proteomics, the Buck Institute has combined its expertise in chemistry, cell biology, and molecular therapeutics into a single program focusing on understanding human aging and longevity. Gibson explained further why the Buck established this center, “We saw the need to combine all our technologies together in one place. We wanted to foster common workflows and informatics procedures.” In setting up the Center, Gibson and Ramanthan consolidated all of the Buck’s mass spectrometry instrumentation (used to identify and quantify proteins and metabolites) into one area so that they could conduct their experiments more efficiently. After installing and fine-tuning their instruments, they began tackling a number of pioneering aging-research projects in partnership with labs at the Buck and other universities.

 Cutting-edge projects underway

Brad GibsonIn collaboration with colleagues at the Buck Institute and the University of Iowa, Ramanathan and Gibson are attempting to identify novel biological targets for maintaining proper muscle function that may lead to treatments for sarcopenia, a disease of muscle wasting. They are treating both fruit fly and mouse models with drugs known to affect longevity and monitoring what metabolites and proteins are produced. By isolating proteins and metabolites from these model organisms treated with various drugs, they can find and compare biological profiles of healthy versus diseased or aging muscle tissues. 

The Center is also studying age-related macular degeneration (AMD), a disease that results in vision loss over time and is a major cause of blindness and visual impairment in adults. In collaboration with Dr. Deepak Lamba’s lab at the Buck, the Center is using a novel 3D human stem cell-derived model of AMD that contains the three main tissue types found in the human eye. The 3D eye can be treated with environmental stressors to simulate macular degeneration in a dish. Scientists can then elucidate the mechanisms behind AMD by determining what proteins and metabolites are expressed in response to both stressors and in steady state conditions. Their ultimate goal is to identify drug compounds that can promote cell survival in their eye model.

Other ongoing projects in the Center focus on cancer, diabetes, Progeria (accelerated aging), Alzheimer’s and Parkinson’s disease, and cellular senescence (aging on a cellular level – when cells stop dividing and produce pro-inflammatory factors). Additionally, the Center is using various invertebrate and vertebrate models to compare normal versus diseased and young versus old states with the goal of discovering novel proteins and metabolites that play important roles in aging and age-related diseases.

Donor support needed to help the program grow

While many exciting discoveries have already been made, the Center is still in its infancy. Gibson and Ramanathan emphasized that while the Institute has substantially invested in their center, there is still strong need for outside funding to move the Center forward and fully integrate its capabilities. Further monetary support would allow for additional instrumentation, software essential for data analysis, and additional researchers and bioinformaticians to conduct experiments and crunch data.  Indeed, integrating a bioinformatics platform into the Center is still a huge challenge. Ramanathan and Gibson plan to work closely with Sean Mooney’s bioinformatics group at the Buck and Agilent Technologies, a Santa Clara based company that makes scientific instruments, to establish a solid platform to process biological data.

The future looks bright for the Buck’s new Center. Research papers will soon be published based on work produced from the Center and there are plans to hire additional specialists and purchase more instruments and robotics, if proper funding can be secured.

The new Center for metabolomics and proteomics will uniquely place the Buck Institute at the forefront of aging research by providing an integrative platform of cutting-edge technologies that will answer fundamental questions of aging at the molecular level. One of the first of its kind, this center will serve as a model for other institutes and universities and will greatly impact the field of aging research.

Those interested in supporting the new Center should contact Carlotta Duncan, PhD, Director of Scientific Advancement at 415-209-2267 or cduncan@buckinstitute.org

Written by Karen Ring, PhD

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