Dr Edwina McGlinn - Researcher Profile

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Address

Faculty of Medicine, Nursing & Health Sciences
Monash University, Clayton

Biography

RNA: DNA’s lesser-known companion

DNA, RNA and proteins are the three key macromolecules for all known life. While science has recognised the importance of DNA for more than 100 years, it has not fully appreciated the diverse roles of RNA (ribonucleic acid) until quite recently. During her first six months at the Australian Regenerative Medicine Institute, Dr Edwina McGlinn has made great progress working with short pieces of RNA, known as microRNAs.

RNA is similar to DNA in the sense that it consists of a chain of components called nucleotides. RNA’s nucleotide sequence allows it to encode genetic information, while some RNA molecules can link amino acids to form proteins. MicroRNAs are common in many human cell types and can play a role in target degradation and gene silencing. Edwina says her focus has shifted to microRNAs in recent years, partly due to their involvement in gene silencing. 

“It is well established that certain RNAs are a key intermediate step between DNA and proteins, but it turns out that some RNAs never make protein and actually regulate gene expression directly,” Edwina explains. “It was a big shift in the central dogma. Now the challenge is to work out what microRNAs are doing in the body.

“The same 25,000 genes are present in the DNA of each cell. However, our liver cell is very different from a brain cell. This is because not all genes are active in every cell. Each cell knows what to be because the genes it turns on and off leads to a unique protein output. It gives cells their identity and makes them functional in the right area. 

“If this unique “code” of gene expression within a cell is altered, things can go wrong and may lead to disease. It is therefore very important to understand all factors that regulate gene expression, and this now includes microRNAs.

“We didn’t know anything about microRNAs 20 years ago but this field of research has exploded, particularly over the last 10 years. Our lab has developed technologies to assess microRNA function in vivo, in a developmental context. Nobody had really done it in this way before,” she says.

Edwina is also trying to develop a better understanding of the genetic networks that control limb formation. She says the limb is a great basis for this research.

“The limb is a classic model for understanding how cells interact with each other and how genetic systems interact in a three-dimensional space. We can add or remove a gene and see what happens to the whole genetic network, and importantly, the consequences later in development. 

“The limb model has been used for decades, and we’re now using more modern genetic techniques to look at classic developmental experiments. 

“We hope that the basic developmental questions we are asking will also shed light on genetic pathways that may be involved in disease later in life,” Edwina says.

Understanding how a limb grows in the first place is also likely to help other researchers investigating limb regrowth techniques in humans, but Edwina concedes this is a long-term goal.

“It’s not going to happen tomorrow, but a lot of great work is happening in that area.”

Qualifications

DOCTOR OF PHILOSOPHY
Institution: University of Queensland
Year awarded: 2004
BSC-HONOURS
Institution: University of Queensland
Year awarded: 1995

Publications

Book Chapters

Mansfield, J.H., McGlinn, E., 2012, Evolution, expression, and developmental function of Hox-embedded miRNAs, in Current Topics In Developmental Biology [P], eds PM Wasserman & O Pourquie, Academia Press, USA, pp. 31-57.

McGlinn, E., Mansfield, J., 2011, Detection of Gene Expression in Mouse Embryos and Tissue Sections, in Methods in Molecular Biology - Vertebrate Embryogenesis, eds FJ Pelegri, Humana Press, USA, pp. 259-292.

Journal Articles

Hu, J.K., McGlinn, E., Harfe, B.D., Kardon, G., Tabin, C.J., 2012, Autonomous and nonautonomous roles of hedgehog signaling in regulating limb muscle formation, Genes & Development [P], vol 26, issue 18, Cold Spring Harbor Laboratory Press, USA, pp. 2088-2102.

Heimberg, A., McGlinn, E., 2012, Building a robust A-P axis, Current Genomics [P], vol 13, issue 4, Bentham Science Publishers Ltd, Netherlands, pp. 278-288.

Town, L., McGlinn, E., Davidson, T., Browne, C.M., Chawengsaksophak, K., Koopman, P.A., Richman, J.M., Wicking, C., 2011, Tmem26 is dynamically expressed during palate and limb development but is not required for embryonic survival, PLoS ONE [P], vol 6, issue 9 (Art. No: e25228), Public Library of Science, USA, pp. 1-9.

Haramati, S., Chapnik, E., Sztainberg, Y., Eilam, R., Zwang, R., Gershoni, N., McGlinn, E., Heiser, P., Wills, A., Wirguin, I., Rubin, L., Misawa, H., Tabin, C., Brown Jr., R., Chen, A., Hornstein, E., 2010, miRNA malfunction causes spinal motor neuron disease, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 107, issue 29, National Academy of Sciences, USA, pp. 13111-13116.

Mao, J., McGlinn, E., Huang, P., Tabin, C., McMahon, A., 2009, Fgf-dependent Etv4/5 activity is required for posterior restriction of Sonic Hedgehog and promoting outgrowth of the vertebrate limb, Developmental Cell [P], vol 16, issue 4, Cell Press, USA, pp. 600-606.

McGlinn, E., Yekta, S., Mansfield, J., Soutschek, J., Bartel, D., Tabin, C., 2009, In ovo application of antagomiRs indicates a role for miR-196 in patterning the chick axial skeleton through Hox gene regulation, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 106, issue 44, National Academy of Sciences, USA, pp. 18610-18615.

Butterfield, N., Metzis, V., McGlinn, E., Bruce, S., Wainwright, B.J., Wicking, C., 2009, Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb, Development [P], vol 136, issue 20, Company of Biologists Ltd, UK, pp. 3515-3524.

Town, L., McGlinn, E., Fiorenza, S., Metzis, V., Butterfield, N., Richman, J., Wicking, C., 2009, The metalloendopeptidase gene Pitrm1 is regulated by hedgehog signaling in the developing mouse limb and is expressed in muscle progenitors, Developmental Dynamics [P], vol 238, issue 12, Wiley-Blackwell, USA, pp. 3175-3184.

McGlinn, E., Richman, J., Metzis, V., Town, L., Butterfield, N., Wainwright, B.J., Wicking, C., 2008, Expression of the NET family member Zfp503 is regulated by hedgehog and BMP signaling in the limb, Developmental Dynamics [P], vol 237, issue 4, Wiley-Blackwell, USA, pp. 1172-1182.

Scherz, P., McGlinn, E., Nissim, S., Tabin, C., 2007, Extended exposure to Sonic hedgehog is required for patterning the posterior digits of the vertebrate limb, Developmental Biology [P], vol 308, issue 2, Academic Press Inc Elsevier Science, USA, pp. 343-354.

McGlinn, E., Tabin, C., 2006, Mechanistic insight into how Shh patterns the vertebrate limb, Current Opinion in Genetics and Development [P], vol 16, issue 4, Current Biology Ltd, UK, pp. 426-432.

McGlinn, E., van Bueren, K., Fiorenza, S., Mo, R., Poh, A., Forrest, A., Soares, M., Bonaldo, M., Grimmond, S., Hui, C., Wainwright, B., Wicking, C., 2005, Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development, Mechanisms of Development [P], vol 122, issue 11, Elsevier Science BV, The Netherlands, pp. 1218-1233.