Abu Ali Ibn Sina, Laura G. Carrascosa,* Matt Trau*

 

Center for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology (AIBN), Corner College and Cooper Roads (Bldg 75), The University of Queensland, Brisbane QLD 4072, Australia
Tel: +61-7-33464178; Fax: +61-7-33463973
Email: a.sina@uq.edu.au (AAIS); l.carrascosa@uq.edu.au (LGC); m.trau@uq.edu.au (MT)

 

The analysis of DNA methylation is becoming increasingly important both in the clinic and also as a research tool to unravel key epigenetic molecular mechanism in biology. Current methodologies for the quantification of regional DNA methylation (i.e., the average methylation over a region of DNA in the genome) are largely affected by comprehensive DNA sequencing methodologies which tend to be expensive, tedious and time-consuming for many applications. Herein, we utilize the interfacial chemistry between gold and DNA to detect DNA methylation and to deliver a new biomedical tool for epigenetic analysis. In contrast to current strategies, the interfacial bio-sensing approach utilizes the direct interaction of biomolecules (e.g. DNA) with the metal surface (i.e., gold) as a mean to extract methylation information from their sequence. However, the nature of DNA-bare gold affinity (i.e., adsorption) has long been regarded as "nonspecific" and "difficult to control". Recent advances in this field have suggested that this is a base dependent phenomenon and follows the trend Adenine(A)> Cytosine(C)> Guanine(G)> Thymine.1 Since this interaction is highly sequence dependent, it provides a new capability to detect DNA methylation by simply monitoring the relative adsorption of bisulphite treated and asymmetric PCR processed methylated (guanine enriched) and unmethylated (adenine enriched) DNA onto a bare gold chip. Because the differential adsorption of DNA towards gold enables a direct read-out of regional DNA methylation, the current requirement for DNA sequencing is obviated. Over the last 2 years, we have extensively explored this methodology for detecting regional DNA methylation of CpG clusters located in different genes within several breast cancer cell lines using optical2 and electrochemical read-outs.3,4 This presentation shall review these developments highlighting the applicability of interfacial biosensing via bare gold-DNA affinity for detecting DNA methylation with single CpG site resolution. We anticipate that the simplicity of this method, along with the high level of accuracy for identifying the methylation status of cytosine in DNA could find broad application in biology and diagnostics.

 

References:

1Kimura-Suda, H.;  Petrovykh, D. Y.; Tarlov, M. J.; Whitman, L. J.  J. Am. Chem. Soc. 2003, 125, 9014-9015. Base-dependent competitive adsorption of single-stranded DNA on gold.

2Sina, A A. I.;  Carrascosa, L. G.; Palanisamy, R.;  Rauf, S.;  Shiddiky, M. J. A.; Trau, M.  Anal. Chem. 2014, 86, 10179−10185. Methylsorb: a simple method for quantifying DNA methylation using DNA-gold affinity interactions.

3Sina, A A. I.;  Howell, S.; Carrascosa, L. G.; Rauf,  S.; Shiddiky, M. J. A.; Trau, M. Chem. Commun., 2014, 50, 13153--13156 eMethylsorb: electrochemical quantification of DNA methylation at CpG resolution using DNA–gold affinity interactions.

4Koo, K. M.; Sina, A A. I.;  Carrascosa, L. G.; Shiddiky, M. J. A.; Trau,  M.  Analyst, 2014, 139, 6178-6184. eMethylsorb: rapid quantification of DNA methylation in cancer cells on screen-printed gold electrodes.

Biographic Details

Name: Abu Ali Ibn Sina

Title: Mr.

Affiliation, Country: Center for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane QLD 4072, Australia

Phone: +61 7 3346 4161  Fax: +61733463973 E-mail: a.sina@uq.edu.au

Research interests: Interfacial biosensing, DNA methylation, gold-DNA affinity, Cancer Diagnostics

 

Abu Ali Ibn Sina has recently submitted his PhD thesis from the Centre for Personalized Nanomedicine, Australian Institute for Bioengineering & Nanotechnology (AIBN), The University of Queensland. He received his B.Sc. (Hons) and M.Sc. from Shahjalal University of Science and Technology, Bangladesh. He is also holding a position of Assistant professor (Currently on study leave) at the department of Biochemistry and Molecular Biology, Shahjalal University of Science & Technology, Bangladesh. Prior to joining at Shahjalal University, he served at Berger Paints Bangladesh Limited as a Chemist-R&D. He has wide range of experience with different job environment including industry, teaching and research. The main focus of his research is “Detecting DNA methylation at the gold interface: A gateway towards next generation cancer diagnostics.” He published many research articles in reputed scientific journals and presented in several national and international conferences.