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Soon Rachelle Balez will set sail for Antarctica, a departure from her usual lab work but a voyage of her childhood dreams. She has made it as far as Ushuaia before, the port city at the tip of Argentina, on her gap-year travels. Now, in the midst of her PhD, Rachelle has been chosen to join Homeward Bound, a year-long leadership program for female scientists that culminates in a three-week expedition to the Earth's southernmost continent.

"From when I was a little girl, watching David Attenborough documentaries, I loved anything to do with the environment, nature and Antarctica. My dad is an artist and so is my mum. I don't think science is something that they imagined their daughter doing but in saying that, from the get-go, they nurtured my curiosity - that was the biggest thing," she says fondly.

Growing up in Scarborough, beneath the Illawarra escarpment and with the Pacific Ocean below, Rachelle was drawn to the natural world. She followed her curiosity through rock pools and rainforests, wanting to understand how everything in the environment coexists together. This led her to study environmental science at the ¾«¶«´«Ã½ of ¾«¶«´«Ã½, concentrating first on ecology.

But along the way in her undergraduate studies, which also included a second major in visual arts, Rachelle was side-tracked by her interest in molecular biology and genetics - the inner workings of the cells in our bodies and the blueprint that they follow. She now studies Alzheimer's disease using stem cells that were once skin cells, now reprogrammed to be neurons, or nerve cells.

 
^{PhD student Rachelle Balez.} 

Understanding Alzheimer's

is a neurodegenerative disease that over time causes changes to neurons in the brain. Their function is compromised - exactly how is what scientists are investigating - and the disease slowly derails memory, thinking and behaviour. While Alzheimer's can sometimes be traced through families who have a rare genetic predisposition to the disease, most cases of Alzheimer's are sporadic - that is, it appears in a person with no family history of the disease. Here, a combination of environmental and genetic risk factors is at play.

"It was just after her 80^th birthday that we realised that something had shifted mentally," says Rachelle of her Dutch grandmother, who passed away earlier this year of Alzheimer's disease. "It was heartbreaking to see the slow decline of a woman, who was once so powerful and strong, just fade into the background. In the last few years, she didn't know who I was."

Like other neurodegenerative diseases that lie in waiting, Alzheimer's starts to develop many years before the first symptoms arise. "Small molecular changes [in the brain] might direct you down the path to Alzheimer's disease in later life," Rachelle explains. This makes it very difficult to study the early stages of the disease.

Another hurdle to studying Alzheimer's disease is that living human brain cells are simply unattainable. Where someone with cancer may be able to donate tissue from a recent operation or biopsy to research, this is not possible for people living with neurological diseases like Alzheimer's. Instead, scientists have pieced together the story of Alzheimer's disease from post-mortem brain tissue - until (iPSCs) were discovered a decade ago.
 

 

 

 

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Cellular programming

The beauty of stem cells is that they can be reprogrammed, or instructed, to become any cell of the body. Their fate not yet determined, stem cells are malleable, or pluripotent. Unlike embryonic stem cells, iPSCs are derived from mature adult cells. This has been a game-changer for studying the early molecular changes in Alzheimer's and other neurological diseases.

"What we're able to do with iPSCs is take skin cells from people who have Alzheimer's disease, reprogram them back into a stem cell and differentiate them, or direct the way the stem cell grows - and for us that's into a brain cell. This gives us human brain cells in a dish, a living model to work with," Rachelle says. It can take up to six months to reprogram and characterise one cell line. Rachelle is working with four and aims to create another three cell lines for her research.

Rachelle looks at the way neurons talk to each other, surveying the behaviour of skin-cells-turned-neurons from people with Alzheimer's and others without. She suspects that cell signalling has gone haywire in Alzheimer's disease.

In the brain, neural networks encode memories and learning pathways. Neurons transmit messages to neighbouring nerve cells, and onto other cells further afield in the body, like muscle cells and gland cells, by shuttling chemical compounds. One of the main chemicals involved in cell signalling between neurons is calcium.

Using a technique called calcium imaging, Rachelle has found that the Alzheimer cell lines are hyper-excitable compared to neurons grown from healthy people. "The Alzheimer's cells are flashing, always talking to each other," she says, "which means they are letting too much calcium into the system."

Rachelle speaks about her research with ease. She loves that her project delivers lots of visual results, like the microscopic images of her energetic cells and the grainy photographs of squiggly chromosomes from her cell lines. Called karyotypes, these photographs are the final checkpoint of the integrity of each iPSC-derived neuronal cell line after months of work.

Family connections

Given that her family has been touched by the disease, when the opportunity to study it appeared, Rachelle knew she had found her place in the lab. "I had always been fascinated by stem cells but there was also the connection to my oma. The project pretty much had my name on it," she says.

Rachelle recounts stories of her Dutch grandmother, who was born in the Netherlands and immigrated to Australia after World War II, with tenderness and a warm smile. "[My grandparents] were thrown into a country on the other side of the world. My opa built their house in Oyster Bay, south of Sydney, and they brought up two girls. My oma carried that class and strength through her life," Rachelle says.

Now midway through her PhD, Rachelle carries her oma's spirit in conversation and takes her tenacity to her work. Rachelle has the self-assurance of someone who has mapped out a plan and is now executing her work, yet she is realistic about the demands of research. "Science is slow and thorough," she remarks.

Women leading in the lab

When it comes to building a career in science, women also face many barriers along the academic pathway and significantly fewer female researchers are promoted to senior academic roles. So, Rachelle is soaking up the experience of her supervisor, , who in a few short years has crafted a thriving lab group at the Illawarra Health and Medical Research Institute.

"Lezanne is fantastic supervisor - not only for the science that she is able to deliver and the project that she offered me, but it's great being a young female scientist [working] with a young female supervisor," Rachelle says. Dr Ooi joined the ¾«¶«´«Ã½ of ¾«¶«´«Ã½ in 2012 and Rachelle was one of her first students. Identifying people who have skills that will benefit the whole group, the Ooi lab has grown and now includes three postdoctoral researchers, four PhD students and more Honours students.

"Lezanne has a good eye for strategy," Rachelle says, "and that's often something that female leaders are criticised of [lacking]. Each person brings a wealth of knowledge and expertise to our lab that we can access, grow and develop." Outside of the lab, Rachelle also draws lessons in leadership from life experiences on the land.

She counts her experience of working as a tour guide in Alice Springs, which she did for a year before embarking on her PhD, as a key lesson on how to approach conversations with people who see the world from a different view.

"When someone challenges my opinions, I get defensive too - it's a natural reflex," she says, smiling.

"It's very hard to take a step back and process different information. You need to give people the space to be vulnerable, to change their mind, or at least accept different viewpoints."

Rachelle is now looking towards Antarctica, taking on board all the lessons she has learnt along the way.

Homeward Bound

The Homeward Bound program is set against the backdrop of Antarctica because regions of the icy continent are displaying some of the seen anywhere on the planet, indicative of the global climate system. Fractures hundreds of kilometres long are that reach out from the Antarctic mainland into the Southern Ocean because of warming sea and air temperatures.

The environment is fragile, a delicate balance of coexistence and ecological niches, and yet we are pushing our planet to the limit. Mother Nature needs her daughters and Homeward Bound is bringing them together - empowering women in science with leadership skills to influence policy and address global challenges.

is the brain-child of Fabian Dattner, partner of the leadership consulting firm Dattner Grant, and Dr Jessica Melbourne-Thomas, a marine ecologist with the Australian Antarctic Division. Over ten years, Homeward Bound will build a 1000-strong collective of women with science backgrounds to lead our planet to a sustainable future. Each participant was selected for their potential to use their scientific knowledge and methods to have an impact on decision making as it relates to the state of our planet.

All over the globe, women are underrepresented in leadership positions - and our planet is suffering for it. "The earth has not been looked after," Rachelle explains. "It has been considered a commodity to be exploited at all costs. We need a change and the strengths that women hold as leaders may be just that."

^{The study of Antarctica and the Southern Ocean provides critical insights into global-scale change.}

Women , such as taking initiative, displaying innovation, building relationships and inspiring others. Men have the upper hand when it comes to strategy but there is much more to good leadership. "Homeward Bound is very much about fostering the community and bringing everyone along together - not having one person out in front dictating decisions but looking at what is best for the collective," Rachelle says.

Taking her place amongst 80 other inspiring women, the second of ten cohorts, Rachelle will participate in online workshops throughout the year. These will be delivered by a global faculty of leaders who are experts in their field, such as Dr Jane Goodall, primatologist and environmental campaigner, and Christiana Figueres, former Executive Secretary of the United Nations Framework Convention on Climate Change.

Come February, further training in leadership and strategic planning, as well as an education program incorporating the most up-to-date research about the state of our planet, will be delivered aboard the vessel bound for Antarctica.

Rachelle has no expectations of what Homeward Bound will bring. "I'm going in with an open mind, feeling slightly intimidated because of the calibre of women involved, and letting the journey take its course," she says. She will have lots of postcards to write on her Antarctic voyage with the recent rush of support and donations through her .

Citing the discovery of the unknown, the chance to meet and listen to interesting people, and opportunities to travel as the reasons why she loves working in science, Rachelle is all set her Homeward Bound adventure.