Nicholas Lab: Epigenetics in Diabetes

Our research

Dr Lisa Marie Nicholas leads the Epigenetics in Diabetes Research Group, which studies the pancreatic islets of Langerhans. These structures contain alpha, beta, delta, epsilon, and pancreatic polypeptide cells that produce glucagon, insulin, somatostatin, ghrelin and pancreatic polypeptide, respectively to co-operatively regulate glucose homeostasis. Specifically, her lab wants to better understand how metabolic signals from the mother e.g., elevated glucose and lipids in obesity and diabetes, alters the development and functional maturation of these cells in the child. This knowledge is important given that individuals born to mothers with obesity and diabetes during pregnancy are at a much greater risk of pancreatic islet dysfunction and, consequently, type 2 diabetes.

By understanding the development of pancreatic islet cells, we will gain insight into how inappropriate metabolic cues during this process can hinder the ability of these cells to meet the challenge of maintaining tightly controlled blood glucose levels over a lifetime.

Highlighted publications

  • Nicholas LM, Nagao M, Kusinski LC, Fernandez-Twinn DS, Eliasson L, Ozanne SE. Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice. Diabetologia. 2020 Feb;63(2):324-337.
  • Nicholas LM*, Valtat B*, Medina A, Andersson L, Abels M, Mollet IG, Jain D, Eliasson L, Wierup N, Fex M, Mulder H. Mitochondrial transcription factor B2 is essential for mitochondrial and cellular function in pancreatic β-cells. Mol Metab. 2017 May 19;6(7):651-663. *co-first author
  • Nicholas LM, Rattanatray L, MacLaughlin SM, Ozanne SE, Kleemann DO, Walker SK, Morrison JL, Zhang S, Muhlhäusler BS, Martin-Gronert MS, McMillen IC. Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin signaling pathways in the offspring. FASEB J. 2013 Sep;27(9):3786-96.

Projects

  • Defining epigenetic networks in pancreatic β-cells driving sex differences in type 2 diabetes risk

    Project available for: Honours and HDR
    Location: SAHMRI and Adelaide Health & Medical Sciences Building
    Research project start: Semester 1 or Semester 2 2024

    Description:
    This project will investigate, using a mouse model, how exposure to maternal obesity alters the relationship between the epigenome, transcriptome and cellular function in pancreatic β-cells of offspring, leading to higher risk of type 2 diabetes (T2D) in males compared to females. Importantly, we will also determine whether methylation and transcription of these genes are also altered in human islets from T2D donors and whether these changes are associated with particular donor characteristics including sex, body mass index and diabetic status i.e. pre-T2D vs. T2D. This will inform us about whether these same genes are also implicated in the development and progression of T2D in humans.

    Skills learned during this project: Working with primary human and rodent islets, animal models of obesity and diabetes and human beta cell lines, molecular biology techniques, computational biology.

  • Investigating the role of DNA methylation in mediating future type 2 diabetes risk in Aboriginal children exposed to maternal diabetes in pregnancy.

    Project available for: Honours and HDR
    Location: Adelaide Health & Medical Sciences Building
    Research project start: Semester 1 or Semester 2 2024

    Description:
    This project seeks to understand the mechanisms behind the disproportionately high rates of type 2 diabetes spanning multiple generations amongst Aboriginal people with a focus on epigenetics. Using next generation sequencing and advanced computational analysis, this project will identify changes in DNA methylation in the blood of Aboriginal children exposed to maternal diabetes in the womb and how this contributes to the greater risk of type 2 diabetes in these children.

    Skills learned during this project: Molecular biology techniques, computational biology.