Understanding how complex interactions between genes and proteins in cells influence an organism's traits and behaviours is what drives Dan Jacobson's work as a computational systems biologist. The researcher and his team integrate Big Data, supercomputing, mathematics, statistics, and biology to study questions in bioenergy, microbial systems, neuroscience, and precision medicine.
Dan Jacobson's work in bioenergy builds on a long-standing research initiative focused on Populus, a fast-growing perennial tree that shows promise as a low-cost, renewable feedstock for bioenergy. A large team of researchers collected data on 28 million genetic variations in Populus as part of the BioEnergy Science Center, with the work now continuing at the Center for Bioenergy Innovation at ORNL.
With this wealth of data and a grant from the Department of Energy's Innovative and Novel Computational Impact on Theory and Experiment (INCITE) programme, Dan Jacobson and collaborators are creating an unprecedented view of the 3D interactions among components of the cellular machinery in poplar.
"We're taking these very large and disparate data sets and integrating them into a whole that nobody really projected", stated Dan Jacobson.
Predicting how genes, proteins, and small molecules interact inside a cell requires the development of new approaches to mining big data with high-performance computing. Using explainable AI, researchers are starting to discover the high-order interactions that their algorithms capture in order to make the results understandable by humans.
Dan Jacobson is using explainable AI to discover molecular interactions in biological systems that lead to the emergent properties of the organism - physical characteristics, diseases, etc., but he noted that the method can be adapted and applied to other projects to accelerate scientific discovery.
"No one complains when you poke a tree", stated Dan Jacobson. "You can learn a lot developing algorithms for a better understanding of plants for bioenergy. We can pivot and apply that knowledge toward projects that are going to positively impact human health. The algorithm doesn't care about the species."
Examining how genetics affects health is the aim of a collaborative project Dan Jacobson is contributing to with support from the U.S. Department of Veterans Affairs and DOE. The project combines genetic, clinical and lifestyle data with the ultimate goal of predicting and diagnosing diseases and tailoring treatments for individuals.
As one of the largest clinical genomics projects in the world, the initiative challenges scientists to use high performance computing and millions of veterans' health data to understand the complex genetic underpinnings that affect medical disorders, drug interactions, drug specificity, and individuals' responses to pharmaceuticals.
Dan Jacobson's interest in the veterans project is both professional and personal as his grandfather, father, brother, and nephew have served in the U.S. armed forces. He has a similar passion for investigating Alzheimers and other neurological disorders.
The human brain is the ultimate complex system, said Dan Jacobson, who took graduate courses in neuroanatomy and neurochemistry as an undergraduate. "It just lit me up", he stated. "And so now, it is always on my radar."
Some of the data sets Dan Jacobson and his team are currently working with came from the Johns Hopkins School of Medicine, where he received his master of science degree in biochemistry and worked as an assistant professor early in his career. In fact, Dan Jacobson pulls data from a wide variety of sources around the globe. Collaborative networks sharing data are essential to modern, large-scale biology. Dan Jacobson has recently been selected to lead an Early Science project on Summit, ORNL's new supercomputer, focused on human systems biology and drug discovery.
It was the Big Data housed at ORNL combined with some of the fastest supercomputers in the world that drew Dan Jacobson to return home to Oak Ridge where he spent his childhood.
Dan Jacobson grew up in a scientific household with his father, Bruce Jacobson, a biochemical geneticist at ORNL, as his role model. The pair had the opportunity to collaborate on a couple of projects together during the early days of the Human Genome Project.
The collaboration took place during Dan Jacobson's first job at the laboratory as an intern before grad school. He worked as a biologist in a physics group, exploring different ways to image and tag biological molecules, after earning his bachelor of science degree in biochemistry at Florida State University.
When Dan Jacobson and his father jointly presented their research at a conference, they often flew from different parts of the world to do so.
Dan Jacobson journeyed to South Africa to help establish national programmes for bioinformatics and supercomputing. While there, he also secured his doctoral degree in computational biology as applied to wine biotechnology.
As the leader of a computational biology group at the Institute for Wine Biotechnology at Stellenbosch University, Dan Jacobson studied, among other things, the grapevine phytobiome, including the plants, soil, environment, and associated microbial communities. He and his colleagues made fundamental discoveries that helped explain variations in wines made from the same cultivar grown in contiguous vineyards but using different farming practices - traditional, organic and biodynamic.
"It was a really convenient excuse to do systems biology out in the field", stated Dan Jacobson, who also appreciates fine wines. "It is one of the few - if any - scientific environments where you can drink the results of some of your experiments."
It turns out that research into wines and grapevines has many parallels in bioenergy applications. In both cases, scientists are looking at similar questions about the growth of biomass and fermentation processes that follow. This made the transition to bioenergy research at ORNL an easy one for Dan Jacobson and several students from South Africa who made the move with him in 2014. This background has also enabled Dan Jacobson and his students to make significant contributions to the ORNL Plant Microbe Interfaces Project that examines the fundamental relationships among plants and microbes to facilitate an understanding of sustainable systems and the use of renewable feedstocks for bioenergy.
Through all the work environments he has experienced and enjoyed - from academia to spin-off companies to non-governmental organisations - Dan Jacobson had been subconsciously missing the interdisciplinary nature of a national lab, he admitted.
"National labs think at larger scales", stated Dan Jacobson. "My group and I are driven by Big Data, big science, and exciting opportunities. We've felt right at home here."