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From a Namaqualand Village to the New Frontier of Medical Research at Stanford

Lydia-Marie Joubert Emerges as South Africa's Renaissance Woman
By Rowan Philp

Lydia-Marie Joubert is at the cutting edge of a field where the “cutting edge” is 5,000 times sharper than a knife. Having produced world-class research in botany, microbiology and microscopy at the University of Stellenbosch for over two decades, Professor Joubert now heads biological scanning electron microscopy at Stanford University.

In 2009 – just four years after her arrival in the U.S. – the 57-year-old scientist won an American Microscopy Society Award for her breakthrough development of new methods to investigate hydrogels; a “one-off” honor that no scientist is allowed to win twice. And four years after that, Joubert used both her “left brain” microscopy skills and her “right brain” creative muse to create an iconic image that helped re-cast the public understanding of the threat of bacteria, through popular magazines like Wired.

She heads up a key discipline at arguably the world’s leading genetic medicine research center, and is helping to pioneer new methods to unlock the biggest secrets from the tiniest features in living things. Here, she collaborates with leading scientists and students in discovering new ways to research and tackle health problems, including hearing loss, sinus-related disorders, stomach cancer and cystic fibrosis.

Now joining the SABLE community, Joubert spent her early childhood years in the tiny Namaqualand village of Wallekraal, in the Northern Cape, and was a primary school student at a farm school in the Knysna Forest.

“We were only 3 students in 1^st and 2^nd grade – two Afrikaans and one English speaking, so classes were all bilingual. My parents were both teachers and instilled in me a love for learning and excellence,” she says.

Joubert told SABLE that she also collaborates closely with the commercial manufacturers of advanced microscopy tools: advising them on the optimal designs and applications needed to tackle some of the most critical research problems facing mankind.

She says: “99% of what I do involves solving biological problems in collaborations, but I’m also actually working with manufacturers to improve the efficiency or features or automation we need."

“In my hydrogel imaging – visualizing wet biomaterials with a specific type of scanning electron microscope called a VP (variable pressure SEM) – I actually I cut my teeth on that in Stellenbosch; we just got a new SEM, and we had a specific focus on bacterial biofilms, which require hydrated conditions to reveal their real ‘in situ’ nature.”

Joubert is also perhaps South Africa’s ultimate Renaissance Woman: a world class research scientist and mother-of-three who writes poetry, plays the piano, rides motorcycles, hikes mountains, seeks cures, and practices kung fu. In fact, this October, she will be hiking the 260km Tankwa Camino Train in the Karoo.

And – yes – she has also won a major “art” award too. Joubert took multiple micrographs of colonies of live and dead bacteria – enlarged 400 times – and superimposed them on a sculpture of a human hand.

With the fluorescent green of the living bacteria dwarfing the red of the dead bugs, Joubert was able to graphically show how microbes – increasingly resistant to anti-bacterial drugs – are “winning the war” between humans and bugs.

In 2013, her image – “The Hand” – won the “People’s Choice” Award in the annual International Science & Engineering Visualization Challenge, which is presented by the journal Science and the US National Science Foundation.

Day to day, Joubert creates 3-D images of things up to 10,000 times smaller than a human hair, and finds novel and potentially life-changing applications from the data. And, in fact, the tiniest things that hairs do – from their secretions to their regenerative gene features – have been a celebrated focus of her research career.

With the official title of senior scientist and electron microscopy (EM) specialist at Stanford’s Cell Sciences Imaging Facility, she works within a molecular and genetic medicine research unit co-founded by Nobel Prize winning biochemist Paul Berg.

Her precise scientific work makes for dizzying reading to non-scientists, but she says: “In collaboration with some extraordinary colleagues, I think the biggest breakthroughs I’ve contributed to have involved hydrogel scaffolds for regenerative medicine, and also the integration of new technologies, especially 3-D applications in electron microscopy. In microscopy you always try to push the limits of resolution – that is in the first place why science moved beyond light microscopy and into electron microscopy, making use of the shorter wavelengths of accelerated electrons over visible light. With the dawn of the molecular era, many novel tools to identify structures and characterize cellular activities were discovered.”

She adds: “Its very inspiring to work with such brilliant minds – but we South Africans don’t always know how intimidating things should seem, so I am not often over-awed, and I think my perspective can be an advantage. Also, we grow up with a lot of freedom to express our individuality – we definitely do not have a homogenized culture that tries to box you in.”

Stanford scientists are leaders in the new national effort – supported by President Barack Obama – to tackle the most complex problem in human history, which has the potential to solve numerous neurological disorders: the mapping of the human brain.

Led by bioengineering genius Karl Deisseroth, Stanford’s brain team have invented two key tools that make the mapping of the trillions of neural connections within the “Human Connectome” possible. One of these tools is called “CLARITY,” which Joubert describes as a method for replacing the opaque fat layers in the brain with a transparent hydrogel, so that we can finally, truly, see inside the brain. Joubert says she and her students are proud to play a role in this historic project.

But Joubert’s truly pioneering role has been in applying some of the powerful new technologies and techniques being developed for the richly funded Connectome project to other, less grandiose medical research: those associated with far less complicated tissues, and which could see new cures in the near term.

Most promisingly: Her team has applied the new tools to breakthrough research on the nasal cavity, and in the inner ear; research which is already suggesting new therapy pathways for sinus diseases and hearing loss.

Joubert says electron microscopy has undergone a series of peaks and troughs as a research field, including prominence in the 1970s, a dip in the late 1980s, and a recent resurgence, partly driven by powerful new molecular techniques and software, and integration of commercial technologies.

“A lot of the protocols we still use were developed in the 60s and 70s, and some of the best hardware tools have been around for a while also. What is novel at the moment is that you can integrate the microscopy technologies and disciplines to find new solutions. Then, of course, digital imaging caused a giant leap in visual sciences. In the eighties a course in EM started with photography principles and most nights were spent in the darkroom, developing film and printing micrographs.”

Despite her original training as a plant scientist, she says she was fortunate to hone her microscopy skills beneath world-class instructors in Stellenbosch in the beginning of her career.

“I was very lucky that I was involved in electron microscopy in the late 70s and 80s in South Africa, when it was not far behind the cutting edge,” she says. "The fundamental work that my PhD adviser, Prof. Jan Coetzee, did then, is still included in EM text books. SA still has a vibrant EM Society with great facilities at most major universities – they are still known in the world.  People there may not have many of the cutting-edge projects I might have here at Stanford, because the application is much more limited in South Africa, but I feel the brainpower is quite similar. Also, the South African curriculum was more diversified, which creates all-rounder researchers, who are good at finding new applications, and thinking multidisciplinary.”

At Stellenbosch, she investigated ecological aspects of antimicrobial resistance, and her research areas included bioenergy production, using techniques that she is now applying to medical research. Joubert found the research environment at Stanford sharply different.

“The biggest adjustment for me is that everything is run almost like a business operation – things are done on a paid-by-the-hour basis, the efficiency of people needs to be really high. You don’t just get to play around with EMs. You really are dedicated as per your defined project. I’m also training students how to use these instruments, and teach them fundamental and advanced EM principles.”

One of Joubert’s strengths is her ability to differentiate between critical research and “gee-whiz” discoveries. She says: “Its important to ask: What do we really need to know, and what are just optional extras?”

Now living in Los Altos, Joubert says she divides her weekend time between family, writing research papers, and her rich group of hobbies: jogging; hiking; piano; and poetry.

“I hope to publish a book of poetry at some point – perhaps something on South Africa!”

But Joubert finds some of the most profound poetry in her EM samples.

“To see the tip links of stereocilia in the inner ear, for instance – it is amazing for me to see these very tiny things, and to see how they evolved for hearing, how everything is perfectly suitable for its application. How form follows function. And simply how beautiful life is.”