Inside the cookbook of genetic recipes
- Wits University
Caitlin Wheeler is a Novartis Next Generation Scientist whose PhD zooms in on confounding questions about autoimmune liver disease.
Do you have a cookbook in your family that’s been handed down from your Grandma to your Mom, to you? Most of us do. To understand genetics, think of that cookbook as the genome. It’s inherited from your family and holds all your DNA.
Within that cookbook (genome), there’s different recipes – one for butter chicken, another for cake – those are the transcriptome. Ribonucelic acid (RNA) holds the specific instructions: two tablespoons of sugar, one teaspoon of salt. That gets baked into the cake, which is the protein, and which carries out all the processes in your body.
“I’m focusing on the RNA and looking at these ‘recipes’,” says Caitlin Wheeler, after that very digestible introduction to Genetics 101.
Mastering pharmacokinetics
Caitlin is a PhD student, jointly at the Division of Human Genetics, Wits Donald Gordon Medical Centre (WDGMC), and the Council for Scientific and Industrial Research (CSIR). She did her Master’s in Genomic Medicine at Wits University — her introduction to precision medicine and clinical research. Using data from the WDGMC paediatric living liver donor transplants, her focus was on researching pharmacogenomics and pharmacokinetics – the absorption, distribution, metabolism, and excretion of drugs.
In 2018, the WDGMC did the world’s first living donor liver transplant from an HIV positive mother to her HIV negative child. This is relevant because in living donor liver transplants, a portion of the liver is taken from the donor and transplanted into the patient. “The donor genetics are therefore also ‘transplanted’ and ‘become’ those of the child, whose diseased liver is removed at the time of the transplant,” says Caitlin. “What’s important then is that we can genotype the donor instead of putting the paediatric recipient through additional blood tests.”
After a liver transplant, it’s important to control the immune system, which is a see-saw balance, Caitlin says: “If you give too little of the drug, the patient is at risk of rejection, you give too much, the patient gets sick from toxicity.”
The clinicians at WDGMC noticed that some children showed lower blood levels of a key immunosuppressant drug that prevents organ rejection. Understanding why became the focus of Caitlin’s Master’s research in pharmacogenomics. Her study showed there were (inherited) genetic causes for these low drug concentration levels.
“From that study, we saw that the genotype for a specific enzyme, called CYP3A5, directly influences the response in paediatric patients to an important immunosuppression medication. All the black African patients in our cohort had the genotype which corresponds to a need for an increased dosage—it predisposes them to needing more of the drug.”
This research was published in the South African Medical Journal with Caitlin as first author. “But what really stuck with me was the ‘why?’,” says Caitlin. So began her PhD odyssey to find out.
Autoimmune hepatitis
“For my PhD, the focus is on a rare autoimmune liver disease called autoimmune hepatitis [AIH],” says Caitlin. She chose to focus on AIH because doctors at WDGMC say it’s a real problem in their clinic.
“We’re seeing patients who come in, and they have advanced progression of disease, and we’re seeing that there is a younger age, as well as a female predominance,” she says. “We don’t understand why autoimmune hepatitis happens. We know it’s the immune system attacking itself and its specific in the liver, but not the specifics of why and how it happens.”
People with AIH may live normal, regular lives – no alcohol or drug abuse, no major illnesses – but then one day they wake up a bit tired, that turns into fatigue, and then other symptoms like a dry mouth and jaundice emerge. “Then, suddenly, they feel really ill, and when their doctor refers them for liver enzyme tests and after a liver biopsy, autoimmune liver disease can be diagnosed.”
Zooming in on single cell sequencing
Returning to the cookbook analogy, Caitlin explains that her PhD focuses on the individual ‘recipes’ (the RNA). “Sometimes what might happen is there’s two spoons of sugar, two spoons of salt, then something goes wrong in the recipe, and that’s what might cause disease,” she says. “That’s the important thing about zooming in: you have the liver, then you have the cell, and then within the cell, you’re looking at the RNA and gene expression.”
This scientific methodology is called single cell RNA sequencing which entails separating out cells into cell type to see how many different cells there are and what might be going wrong in them. “DNA is the double helix. What I’m studying, the RNA with the gene expression, is a single strand,” she says. Her PhD is an investigation into the molecular markers that drive this autoimmune liver disease especially young African women.
African populations are largely underrepresented in global research — especially in the omics space. ‘Omics’ is term encompassing several different technologies such as genomics, transcriptomics, proteomics, metabolomics, etc.
“The omics all have a special superpower,” explains Caitlin. “For example, genomics looks at large amounts of genetic data and can further link this to health trends.”
A study like Caitlin’s PhD has likely not been done in Africa before, and research is limited. To undertake single cell sequencing, she needs skills that are not readily available in South Africa. That’s why pharma giant, Novartis, selected her as one of its Next Generation Scientists.
Next Generation Scientist
Caitlin returned from the three-month training programme at the Novartis campus in Basel, Switzerland, in September 2025. “I was surrounded by experts in single-cell data science, and I gained hands-on experience with large-scale transcriptomic data and building single-cell atlases,” she says.
Single-cell atlases provide insight into cellular diversity across different datasets, technologies, and tissue types. These atlases guide researchers towards understanding disease and discovering high-dimensional drug targets.
She will implement this scarce skill set by contributing to local research projects that aim to map cellular profiles in disease contexts relevant to our population, and specifically to her PhD research on autoimmune liver disease.