In Memory of Mark Hildebrand (1958–2018)

Raffaela M. Abbriano1, Olga Gaidarenko2, and Daniel P. Yee3,4

1University of Technology Sydney, Climate Change Cluster, Australia

2University of California Berkeley, Department of Plant and Microbial Biology, Berkeley, California, USA

3University of Grenoble Alpes, CEA, IRIG-LPCV, Grenoble, France

4European Molecular Biology Laboratory, Cell Biology & Biophysics Unit, Heidelberg, Germany

In August 2018 at the age of 59, Mark Hildebrand passed away at his home in La Jolla, California, 4 years after receiving a cancer diagnosis. Mark confronted the disease with his characteristic humility and patience and approached his life and science with renewed vigor. Mark was a fundamental biologist at heart, allowing curiosity to fuel his exploration of life’s beauty at all scales and inspire his research. His legacy includes a body of scientific publications that touches on all aspects of diatom molecular biology, but especially in the understanding of silica transport, biomineralization, and cell wall architecture.

At the time of his diagnosis, Mark had just been recognized by the US Department of Energy’s Bioenergy Technologies Office as the top algal biofuel researcher in the nation. As a founding member of the International Conference on the Molecular Life of Diatoms and the California Center for Algal Biotechnology, Mark was at a point in his career to truly realize the potential of diatoms for biotechnology. The publications that flowed from his lab covered tools and approaches for engineering diatom lipid and sugar metabolism to demonstrating the potential of diatoms as factories for inducible protein and vaccine production. All the while, Mark remained an authority on diatom silicon metabolism, with his team putting out original research probing the fundamentals of silicon transport, silica patterning and biomineralization, and comprehensive reviews on the state of the field and prospectives for the future.

Mark on the table with students at the San Diego Self-Realization Fellowship.

In his personal time, Mark’s passion for art and music thrived. He was an avid guitarist, drawing some of his inspiration from the likes of the jazz musician Pat Metheny, and had a modest guitar collection at home. In addition to his various guitars, Mark played other instruments such as the harmonium and tabla and taught a music class for teens at the San Diego Self-Realization Fellowship. Always eager to learn more and have new experiences, Mark took up conga drum lessons from one of his PhD students and once organized the lab to go sky sailing in a glider plane over the California desert. Mark also spent time designing his home, including the construction of a beautiful nature-inspired glass arrangement for his patio. His vibrant creation became a reflection of his appreciation of the beauty in the world and a place he could share with friends and colleagues. The years after Mark’s diagnosis may have been his most imaginative and creative yet, and it is an understatement to say he had much more to give to this world and to science. In the remainder of this memorial, we hope to honor Mark’s memory and provide a glimpse into the life and career of one of diatoms greatest admirers.

Born in 1958, Mark was a New Jersey native and received a BS in Chemistry from SUNY Syracuse in 1980. He went on to carry out his PhD in the lab of Prof. Don Bourque at the University of Arizona to understand the genetic structure and content of the tobacco chloroplast genome. Prior to the availability of advanced DNA sequencing technology, Mark used classic molecular techniques to deduce a detailed physical map of the tobacco chloroplast DNA and discovered a case of trans-splicing in the maturation of ribosomal protein (rps12) transcripts encoded in the chloroplast genome.

Mark at the Grand Canyon around the time of his PhD (Photo credit: Hildebrand Family).

After completing his PhD in 1987, Mark joined as a post-doc in the lab of Prof. Benjamin E. Volcani in Hubbs Hall at the Scripps Institution of Oceanography (SIO). Ben Volcani was renowned for discovering microbial life in the Dead Sea and was a pioneer in the field of silicon metabolism. With skills homed in molecular biology, Mark’s arrival would help advance marine biology research at SIO:

Mark knew how to “do molecular biology” – manipulate DNA and RNA and identify genes and get sequence info. My lab started doing DNA and sequencing about 1987 and we were asking Mark how to do things every day. Mark had the recipe for what he called “magic buffer” in which every restriction enzyme would function. There were no kits, we made every solution ourselves. Without Mark’s knowledge gained during his Ph.D. research at Arizona we would have had a difficult time, and so would all Scripps researchers who were going into gene discovery. The standard answer to any question about a method was, “no, I don’t know how to do that, but go ask Mark, he’ll know.”

Prof. Vic Vacquier
Scripps Institution of Oceanography

While Mark was clearly making an impact in Hubbs Hall, he was being equally inspired by Ben Volcani’s investigations of silica metabolism and the complexity of diatom biology. Together, Mark and Ben would discover diatom plasmids with open reading frames and transposable elements, laying the early groundwork that would enable the manipulation of diatom genes. As Mark transitioned to becoming a Staff Scientist at SIO, he also began to take-over management of the lab, writing grants as well as advising students and technicians as Ben’s health declined. Meanwhile, Mark was making a name for himself in the diatom field, being the first to identify silicon transporter (SIT) and, soon after, nitrate transporter (NAT) genes in Cylindrotheca fusiformis.

An arrangement of diatom frustules resembling the SIO logo commissioned by Mark.

After Ben’s passing in 1999, Mark transitioned fully to leading his own lab at SIO. Mark built a team with expertise in the areas of advanced imaging, genetic engineering, and genomics that enabled him to pursue fundamental questions in diatom biology. In particular, he was fascinated by the intricate patterning of diatom frustules and the molecular mechanisms that define the silica structure. Although it is a complex research topic filled with many unknowns, Mark was drawn to the challenge. He loved to pursue out-of-the-box lines of thought, many of which led him to combine state-of-the-art imaging and molecular tools with the synchronization of cell cultures through silicon starvation to enable correlating gene expression, cellular metabolism, and frustule biosynthesis with the cell cycle. Through the years, Mark’s work resulted in important discoveries in diatom silicic acid transport and cell wall formation, including the functional characterization of key enzymes involved in silica cell wall patterning and biomineralization. Following the sequencing of the Thalassiosira pseudonana genome and the advent diatom genetic manipulation, Mark also began to envision the potential applications of engineered diatom silica for nanomaterials and nanotechnology.

Mark with fellow silica scientists Kenneth Sandhage and wife (Katherine), and Nils Kröger during the 2005 Pacifichem meeting in Hawaii. (Photo credit: Nicole Poulsen)

Mark was keenly aware of the potential biotechnological applications of algae and was a founding member of the California Center for Algae Biotechnology (Cal-CAB), a consortium that develops and supports collaborations between algae researchers in academia and industry. In his own lab, Mark developed an active program around diatom biofuel research, investigating the regulation of diatom carbon metabolism and ways to improve microalgal lipid productivity. Discoveries by his team led to important insights into the dynamics of carbon utilization and storage in diatoms, genome sequencing of key oleaginous algal species, and identification of lipid catabolism as a genetic target to increase lipid content in diatom cells. These efforts culminated in Mark’s lab being named the top algae biofuel program in the United States by the U.S. Department of Energy. Mark was excited about the future application of algae, and his legacy includes the development of many novel tools for genetic engineering and protein expression in diatoms. Until his passing, Mark’s lab was actively engaged with academic and industry partners on improving algal biomass yields for biotechnology and investigating diatom-based vaccines for applications in aquaculture.

Sky sailing with the lab in 2014 (from left-to-right) Jessica Traller, Olga Gaidarenko, Raffaela Abbriano, Sarah Lerch, and Mark. (Photo credit: Sarah Smith)

More impactful than his research was his influence on everyone that had the opportunity to work with him. Mark was committed to his role as a mentor and regarded his lab members as part of an extended family. Mark was also selective about his collaborators and those who entered his lab. However, once within his trusted circle, he maintained an opendoor policy and was very generous with his time and energy, always willing to sit down with students to discuss their projects and their futures in science. While Mark was calm and soft-spoken, he never held back on his opinions, and ever the dreamer, it was hard to not get excited with him over even the most modest of results and smallest of details. Mark could also be stubborn at times and held everyone in the lab to a high standard of...