As a student, Jack Walther's friends often came to him when they needed a listening ear, or help with relationship struggles.

This summer, Walther took his fascination with the brain and mood disorders to Dr. Darrell Mousseau's psychiatry laboratory, learning to untangle some of the tiny molecular threads that might explain why depression so often shows up alongside dementia.

Walther and the research team dug into the physical interactions between serotonin and the beta amyloid peptides that build up in patients with Alzheimer's disease. .

He admits going from the classroom to the laboratory felt like a sharp learning curve.

"It was totally different," he said. "It's daunting once you get onto it, but once you get going, it makes a lot more sense and you feel way more comfortable."

Using human embryonic kidney cells, Walther and lab staff used cross-linking chemicals to literally 'catch' proteins interacting.

In this episode, Walther recalls the day Mousseau hustled into the lab, results in hand.

"I could see the excitement in his face and it just made kind of the lab buzz a little," said Walther. "We found there is actually some kind of physical interaction between these beta amyloids and the serotonin receptor."

Mousseau's laboratory is narrowing down biochemical events common to depression and Alzheimer's disease, looking for modifiable targets in the depressed brain that could slow or delay the onset of the neurodegenerative disorder.

Walther said being part of that laboratory work felt 'incredible'.

"I want to bring some good into this world," he said. "I would like to focus on people that struggle to help themselves. Whether that's neurodegenerative or it's people that are just stuck in place and don't know what to do."

He aims to earn his honours degree in neuroscience, then keep pressing on.

"Whichever way that takes me, that's when I'll be happy with what I've accomplished," Walther said.

Eve Simpson knows from experience scientific research doesn't always follow a linear path.

In the first of three student research episodes, the fourth-year biochemistry, microbiology and immunology student looks back at a summer spent decoding Eastern Equine Encephalitis Virus (EEEV) in Dr. Anil Kumar's lab.

Simpson said she loved doing bench research, but felt frustrated in the moments where she hit setbacks and moments of doubt.

"I felt like I was letting everyone down," she said. "But everyone I spoke to said they'd been through that. It's part of being a researcher. That's what drives us to do better and keep being curious and learning."

Simpson realized those failures still tell researchers what doesn't work, and provide data for the greater scientific community.

She is now pursuing her honours degree, and plans to return to Kumar's laboratory as she looks at graduate studies, driven by curiosity and a commitment to public health.

"I want to do better. I want my research to help people and I want to do better for the world," she said.

Jessica Sheldon (PhD) is on a mission to starve out Acinetobacter baumannii —one of the world's most virulent hospital-borne pathogens.

Notorious for its speedy evolution and multi-drug resistance, the hospital-borne bacteria lingers on dry surfaces and infects critically-ill patients, leading to sepsis, pneumonia and high mortality rates.

In this episode, Sheldon delves into the real-life events that drove her to investigate histamine, and its role in bacterial survival and immune response.

In 2022, Sheldon joined the University of Saskatchewan's College of Medicine as an assistant professor of Biochemistry, Microbiology & Immunology -- something she now laughs about after an ill-fated high school placement in an immunology laboratory.

"Cytokine cascades, pathways, the signaling just got way over my head real fast," said Sheldon. "I didn't really know what I was doing."

Sheldon enrolled at Lakehead University, drawn to the tiny pathogens with outsized roles in movies like Outbreak. She estimates she read the book The Hot Zone 20 times.

Her persistence paid off.

"One of my second year microbiology teachers said, 'you know, I think you're kind of good at this. Maybe you should try it as a career.'

Sheldon zeroed in on metals and wrote her doctoral dissertation on the role iron plays in the proliferation of bacteria such as Methicillin-resistant staphylococcus aureus (MRSA).

Today, she studies both Morganella morganii and Acinetobacter baumannii — the multi-drug-resistant bacteria singled out twice in the last decade by the World Health Organization as a 'priority 1-critical pathogen'.

"I'm perpetually fascinated by the idea that something so small can change the course of history," said Sheldon. "And we've seen that recently with COVID."

Sheldon was already studying the metal uptake and signalling systems that grow and sustain A. baumannii when the bacteria ripped through hospitals during the pandemic, attacking Covid-infected patients on ventilators.

By 2023, Sheldon landed a five-year CIHR grant of $900,000 to study A. Baumannii and the way it turns histidine into histamine. Her goal is to pinpoint the way the pathogen uses histamine to evade its host, as it sends out siderophores to steal iron and other nutrients.

The compound appears to serve as a signalling mechanism for both the host and the invading pathogen, she said.

"We know the bacteria are using histamine in the synthesis of these molecules to get iron, but they're also secreting it into the environment. We're not really sure why," Sheldon said.

Her laboratory is working to trace and target those pathways, so researchers can identify and potentially develop new treatments — small molecules or antibody inhibitors that could disrupt multi-drug resistant pathogens.

Beyond A. baumannii, histamine may hold the key to how some of the world's most notorious bacteria grow, spread, and evade immune defences, Sheldon said.

"We're running out of drugs, but there's really not a full appreciation for the fact that we're losing the ability to treat bacterial infections," Sheldon said.

"We need to develop supplementary therapies or alternative therapies."