Understanding cellular and mitochondrial metabolism can provide valuable insights into metabolic changes that occur during disease progression and treatment, and can provide an early warning system for mitochondrial toxicity during drug development. Today, those insights typically are gained through static endpoint measurements of cells’ energy source, adenosine triphosphate (ATP).
To gain that data in real-time, newly formed Biocell Energetics offers a suite of assays to monitor energy flux within cells’ mitochondria as well as the energy emanating from glycolytic pathways. Drug developers can use these kinetic measurements of mitochondrial respiration and glycolysis to identify off-target toxicities early, before molecules advance to clinical development.
Deep mitochondrial Insights
Biocell Energetics focuses on drug discovery toxicology, cellular metabolism, environmental toxicity, and exercise science for professional athletes. Mapping energy flux in real time, rather than as an endpoint, is important because the ATP process is dynamic.
“We’re not just measuring toxicity of mitochondria,” Jonathan Barlow, PhD, founder of the company, tells GEN. “We’re also measuring the glycolytic function of the cells.” Therefore, scientists can measure a cell’s metabolic flexibility in response to a compound.
For drug discovery toxicology, he continues, “Not only can we measure and screen compounds for toxicity, we can identify where [in the cell] the toxicity is likely arriving, the magnitude of the toxicity, and whether this changes a cell’s ATP supply flux. With downstream, standardized analysis we can get a better idea of what that compound is doing to the mitochondria. This is all achieved on living intact cells in real time.”
Barlow says this capability is particularly relevant to cancer therapeutics. In targeted cancer therapies, he explains, knocking out a tumor’s presumed energy pathway may not kill the tumor cells. Instead, they adapt to the environment by taking energy from other pathways.
“Going into the energetics at this level provides an overview of what’s going on, not just from the energy that’s coming from mitochondria, but also energy that’s coming from glycolytic pathways,” Barlow says. With that, “You can learn what happens if you start knocking out these pathways.”
What’s new in energetics
The technology to measure cellular energetics itself is available in some academic institutions, and some companies offer a standardized assay for specific cell models—“typically toxicity models,” Barlow says. Biocell Energetics’ contribution to the field is making and commercializing bespoke assays that measure cellular energetics in real time.
Barlow partners with clients, including pharmaceutical companies and contract research organizations (CROs), to develop energetic measurement assays for their own models and cells, tailored to the treatments and genetic modifications they are using. As a consultant, he helps design experiments and adapts or develops fit-for-purpose protocols that address fundamental concerns.
“This is something I’m passionate about,” notes Barlow. “I feel my expertise over years of working with a range of technologies, cell models, and cell types can really help.” Biocell Energetics offers feasibility testing for its protocols and services, as well as assays because, as he points, out, “There isn’t a one-size-fits-all approach.”
Incubated in 2024
Biocell Energetics was formed in 2024 as an operating division of the University of Birmingham Enterprise. This business incubator supports academic entrepreneurs with mentoring, advice, and training, as they test the waters and establish a trading history before deciding whether to spin out a company.
The fledgling business is funded by the University of Birmingham in the UK, Barlow’s personal investment, and some projects with CROs. To reach the next business development stage requires broadening awareness of the technology and its capabilities and attracting pre-seed investments and innovation grants.
“As we generate revenue, we can start looking at employing research staff,” says Barlow.
Measuring organoids and more
Currently, Biocell Energetics is working to develop and adapt its cellular energetics technology to organoids and other 3-dimensional cell models.
One of the challenges with organoids involves the ability of oxygen to diffuse to the cells at the center of the model, Barlow points out. That constraint also poses challenges when measuring cellular energetics with extracellular flux measurements. Consequently, he says, “You can probably ask questions around mitochondrial function,” but measuring glycolytic responses within organoids remains problematic.
The company is developing testing methods to address this, and, therefore, enable reliable measurement of both mitochondrial and glycolytic energetics in organoids.
For the field of exercise science, Barlow also is approaching professional football (soccer) sports teams in the U.K. to determine how cellular energetics may improve training regimens. “There is not a good marker for over-training athletes,” he points out, “and over-training can lead to immune suppression.”
Measuring the intracellular energy flux of immune cells could become that marker. “Immune cells of an immunosuppressed athlete would have a different metabolic signature [different energy flux],” Barlow explains, than those of a normal healthy athlete.
It is also possible that extracellular flux analysis could identify an activated immune system and thus predict inflammation or infection risks before symptoms presented. To get the data needed to make this approach meaningful on a practical level, he advocates challenging the immune system and then monitoring the energetic profile of the immune cells as they transition from a quiescent to an activated state. Early-stage research is underway in that area at the University of Birmingham.
Energetics technology also has the potential to eventually be used to identify blood-based biomarkers. Ultimately, such biomarkers could be used to metabolically profile the health of an individual. For example, he says, “Because peripheral blood mononuclear cells pass through all the tissues in the body, they can often show signs of inflammation [and could possibly] relay information from a given tissue in the body.”
Whether cellular energetics monitoring could pick up any differences in the early stages of disease development remains unknown. For that, according to Barlow, “we need bigger data sets.” Some of that data could come from colleagues at the University of Birmingham who are studying kidney disease patients.
At this point, he says, funding is needed to support more R&D that will lead to additional models.
