Xie earned her PhD in biology from the University of Utah in 2004 and where she remained as a postdoc for several years. At the time, she never imagined herself working industry. Yet to her surprise, she amassed extensive experience in biotechnology. In her first foray from academia, she taught eighth-grade science and helped build the charter school’s AP biology program.

While she loved teaching, Xie always felt the urge to venture out and gain experience in molecular biology which she also enjoyed. As such, new technological developments in a local biotechnology startup, IDbyDNA, presented her call to action. She recalls “the startup company was pushing for a new technology that was obviously going to be the future. Now the question was, who was going to make it a reality? Why not us?”

To finally embrace the uncertainty of industry was scary, but Xie knew this was her time to act. “I can always go back to teach, but this leap of faith, if I didn’t take it, I may not have another opportunity,” she says. In fact, while learning new skills herself, she never stopped teaching and mentoring others. 

Hypothesis-free Diagnostics

IDbyDNA is a local metagenomics company with an innovative algorithm that simultaneously profiles tens of thousands of microorganisms (or pathogens) in any sample by massive parallel sequencing, known as Next Generation Sequencing (NGS). Xie says this technology is fundamentally different from other available tests because it is hypothesis-free. “We’re not making any guesses, educated or not; we just treat everybody the same, and we sequence everything in there. And by analyzing the sequence in the sample, bioinformatics can tell you what it is. You don’t have to say ‘Tell me if it’s the flu.' It will tell you, ‘No, it’s not the flu, it’s something else.’” 

By taking this approach to diagnosis, IDbyDNA circumvents two major problems. “The first issue is [the] diversity of the potential cause of the disease. The second issue is [one of timing as] some of the really dangerous pathogens that cause diseases such as tuberculosis, can take a long time to grow. By the time you can actually grow it and identify it, the patient's disease has progressed, and, [by then,] they might have been in the ICU for weeks.” 

Hybrid Capture

Though these major concerns were sidestepped, other problems became apparent. “One problem we saw at IDbyDNA was when you get a patient sample and you start to sequence the DNA, the majority of the DNA is the host DNA because the human genome is orders of magnitude larger than the pathogen genome,” explains Xie. “Even a single human cell is going to give you much more sequencing information than the pathogen. So, you actually are not going to have the level of sensitivity you want for it to be clinically applicable.”

To bypass this problem, one can enrich the pathogen signal by selectively pulling the pathogen sequences (with complementary DNA) from the sample before analyzing. The challenge here is that the diversity of the pathogens would require extremely high complexity capturing, which means high-complexity DNA synthesis.

At IDbyDNA, Xie started as a research scientist, co-developing the Explify® clinical diagnostic platform and left as an associate director after six years. The company was eventually acquired by Illumina, a giant sequencing company. 

Her next adventure in industry after IDbyDNA was as principal scientist at GenScript, a company that develops and manufactures gene synthesis products and services used by researchers in academia, pharmaceutics and biotech. Xie joined the Seattle campus because of the CustomArray technology that synthesizes millions of different DNA molecules on a semiconductor chip. This high-complexity, low-cost production of DNA became the natural extension of Xie’s earlier interest.  

“When I went there [Genscript], this was pre-production, and I helped them evaluate and quantify how good they are and help them improve the product,” says Xie. Her work over nine months resulted in reduced costs and streamlined application of NGS technology in product development. 

Precision Oncology

From GenScript, Xie took the position of senior director of pharma services at NeoGenomics Laboratory, a company dedicated to precision oncology. This newest endeavor is the perfect combination of her other experiences: a hypothesis-free approach applied with hybrid sequencing technology that can provide targeted therapies for cancer patients. At NeoGenomics, biopsies of tumors are sequenced and matched back to the mutation that caused them.

“Then, if the clinician needs to target the specific cancer, they can select suitable drugs that have been approved or are in clinical trials to [make a] recommendation to the patient based on the sequencing results.” This highly targeted therapy means that the patient doesn't have to suffer general chemo, Xie says. She and her team have launched several impactful tests since she joined NeoGenomics. More exciting tests are getting ready for the market. 

Accelerating the pace

It took a while for Xie to leave academia, but she hasn’t looked back since. She has been dedicated to accelerating the pace in the biotech industry, making innovations at the top of the supply chain that impact research in industry and academia further down, or serving patients with state-of-the-art diagnostic technologies. While earning her PhD at the U, Xie never imagined the exciting career she would create for herself. 

“[W]hat I absorbed in school was that there is no value outside academia because everything else is not as scientifically rigorous and not as innovative, not as cutting edge, not at the very boundary of human knowledge.” 

But Heng Xie’s success at all levels of the biotech industry is living proof of the abundant exciting opportunities students have and a testament to the growth of science beyond academia. Her experiences showcase how rigorous research in academia impacts society through the commercialization of innovative technologies. 

by Lauren Wigod 

New research led by the University of Utah and University College London (UCL) has found that plant bacterial pathogens are able to repurpose elements of their own bacteriophages, or phages, to wipe out competing microbes. These surprise findings suggest such phage-derived elements could someday be harnessed as an alternative to antibiotics, according to Talia Karasov, an assistant professor in the U’s School of Biological Sciences.

This result was hardly what she expected to find when she embarked on this research with an international team of scientists. Microbial pathogens are all around, but only a fraction of the time do they sicken humans, other animals or plants, according to Karasov, whose primary research interest is in interactions between plants and microbial pathogens. The Karasov lab is seeking to understand the factors that lead to sickness and epidemics versus keeping the pathogens in check.

“We see that no single lineage of bacteria can dominate. We wondered whether the phages, the pathogens of our bacterial pathogens, could prevent single lineages from spreading – maybe phages were killing some strains and not others. That’s where our study started, but that’s not where it ended up,” Karasov said. “We looked in the genomes of plant bacterial pathogens to see which phages were infecting them. But it wasn’t the phage we found that was interesting. The bacteria had taken a phage and repurposed it for warfare with other bacteria, now using it to kill competing bacteria.”

A thale cress specimen collected in 1866 in Germany and preserved in a herbarium in Tubingen. Credit: Burbano lab, University College London.

Mining herbarium specimens for their microbial DNA

Burbano has pioneered the use of herbarium specimens to explore the evolution of plants and their microbial pathogens. His lab sequences the genomes of both host plants and those of the microbes associated with the plant at the time of collection more than a century ago.

For the phage research, Burbano analyzed historical specimens of Arabidopsis thaliana, a plant from the mustard family commonly called thale cress, collected in southwestern Germany, comparing them and the microbes they harbored to plants growing today in the same part of Germany. Lead author Talia Backman wonders if tailocins could help solve the impending crisis in antibiotic resistance seen in harmful bacteria that infect humans.

“We as a society are in dire need of new antibiotics, and tailocins have potential as new antimicrobial treatments,” said Backman, a graduate student in the Karasov lab. “While tailocins have been found previously in other bacterial genomes, and have been studied in lab settings, their impact and evolution in wild bacterial populations was not known. The fact that we found that these wild plant pathogens all have tailocins and these tailocins are evolving to kill neighboring bacteria shows how significant they may be in nature.”

Discover the full story behind bacteriophages and their antibiotic potential by Brian Maffly at @The U. More on this story at earth.com.