Nanotechnology in Genomics

1. Group S2 Chris Heflin Mike Jones Rachael Houk Nanotechnology in Genomics

2. Genomics is the study of all the genes of a cell, or tissue, at the DNA, mRNA, or protein levels. The topic focuses on determining the entire DNA sequence of an organism and mapping the genetic material on a fine scale. The application of nanotechnology in genomics is sometimes called “nanobiomics” in medical fields. What is Genomics?

3. Virtually every human ailment has some basis in genes. • Cancer, birth defects, and vulnerabilities to other diseases all can be transferred genetically. • Through a meticulous understanding of genomics, efforts can be made toward removing the propensity for these ailments, and thus make them less common. Why is Genomics Important?

4. How is genomics different than genetics? • Both deal with genetic material, but genetics focuses on one gene at a time. • Genomics focuses on the entirety of the organisms genetic material rather than an isolated gene. Genomics v. Genetics

5. Pharmaceuticals: • Targeted drug development, allowing for more localized treatment. • While most diagnoses are made by analyzing a blood sample, nanobiomics makes it possible to analyze a single cell. Applications of Nanotechnology in Genomics http://mcmannes.files.wordpress.com/2009/11/adhd-drugs-pharmaceutical-774231.jpg

6. Forensics • Allows for more specific DNA identification even when using miniscule traces of genetic material. Applications of Nanotechnology in Genomics http://www.legaljuice.com/dna.jpg

7. Computing • Nanotechnology allows us to create biomolecular devices that are programmable and autonomous. • Programmable meaning the tasks executed can be modified without redesigning the structure. • Autonomous meaning steps are executed and self sustaining. Applications of Nanotechnology in Genomics http://farm3.static.flickr.com/2073/2532729582_0752f41cc2.jpg

8. DNA as a template • DNA is a naturally stable structure. That stability can be harnessed and used to make synthetic molecules. • Nanodevices allow for the construction of molecules by making changes to the DNA template in order to produce the desired properties. Applications of Nanotechnology in Genomics http://www.chrismadden.co.uk/genetics/geneprinter.gif

9. Nanotechnology and the Double Helix By NadrianSeeman Paper 1

10. Develop a way of organizing DNA so that it can be used as a tool, like for nano-machines, or as a structure on which to build crystals for a specific shape Chose DNA because it is very programmable and predictable, simple to synthesize and manipulate, potentially capable of self-replication Goal of the work

11. DNA structure • Energetically favored right spiral double helix (B-DNA) • Less favorable left spiral • Organized spine of phosphate and sugar groups • The “rungs” of the ladder are one of 4 base pairs Background B-DNA Z-DNA

12. Strands of DNA were combined with specific endcaps, which could combine with other strands to form simple structures, similar to marshmallows and toothpicks. These connections were weak and would not make a good structure for crystallization work or scale-up to the macro world Beginning Work From paper FAIL http://www.flickr.com/photos/tstadler/1415613305/

13. Arranged these blocks to make sturdier2-D structures Basic Shapes • Began with work done on DNA barcodes with 5 programmable spaces • DNA strands paired with a double-crossover to make blocks From paper

14. Using programmable end-caps, two strands of DNA can be arranged into something that moves when a condition changes Potential application for nano-tweezers and other simple nano-machines Motion added • Can use different triggers for different locations to get a variety of controlled movements. From paper

15. Drawbacks • DNA must be worked with in aqueous solutions, so the addition of some functional groups is challenging • Current difficulty in promoting self-replication • Potential future • Moving from 2-D to 3-D • Enhance self-replication to reduce manufacturing costs • Integration with nano-electroncics Drawbacks and Future work

16. DNA Nanotechnology and its Biological Applications By John H. Relf and Thomas H. LaBean Paper 2

17. This paper overviews the emerging research area of DNA nanostructures and biomolecular devices. Particularly emphasized are molecular devices that are programmable and autonomous. Paper Overview http://www.svtc.org/images/content/pagebuilder/14163.gif http://www.shoulderdoc.co.uk/images/uploaded/nanobot1.jpg http://www.twine.com/_b/120ln27953vf/b0kw7kcd088fsf

18. Various programmable molecular-scale devices are achievable with various capabilities, including: Capabilities • Computation • 2D Patterning • Amplified Sensing • Molecular Transport Links to Pictures are in Notes

19. There are a wide variety of known enzymes and other proteins used for manipulation of DNA nanostructures that have predictable effects. • Restriction Enzymes • These can cut [double helix break] or nick [single strand break] a DNA backbone at specific locations determined by short base sequences. • Ligase Enzymes • They are able to heal or repair DNA nicks by forming covalent bonds in the sugar-phosphate backbone. • Polymerase • Polymerase can extend a single strand DNA by coupling complementary bases, thus forming a longer sequence of double strand DNA. Manipulation of dna → Links to Pictures are in Notes

20. The previous listed reactions, together with hybridization, are often used to execute and control DNA computations and DNA molecular robotic operations. The restriction enzyme reactions are programmable in the sense that they are site specific, only executed as determined by the appropriate DNA base sequence. The latter two reactions, using ligase and polymerase, require the expenditure of energy via consumption of ATP molecules, and thus can be controlled by ATP concentration. Manipulation of DNA + http://www.hhs.gov/ocr/images/dnastrand.jpg http://comps.fotosearch.com/comtech-robot_~ca_46_4.jpg Link in Notes

21. DNA nanostructures are a multi-molecular complex consisting of a number of single strand DNA that have partially hybridized along their sub-segments. Dna nanostructure John Relf, Thomas LeBean, DNA Nanotechnology and its Applications, chapter 13 in Bio-Inspired and Nano-scale Integrated Computing. Wiley, USA (2007)

22. Figure A illustrates a stem-loop, where single strand DNA loops back to hybridize on itself (that is, one segment of the single strand DNA (near the 5’ end) hybridizes with another segment further along (nearer the 3’ end) on the same single strand DNA strand). Dna nanostructures John Relf, Thomas LeBean, DNA Nanotechnology and its Applications, chapter 13 in Bio-Inspired and Nano-scale Integrated Computing. Wiley, USA (2007) • The shown stem consists of the double strand DNA region with sequence CACGGTGC on the bottom strand. The loop in this case consists of the single strand DNA region with sequence TTTT. Stem-loops are often used as markers for visualizing programmed patterning on DNA nanostructures.

23. Figure B illustrates a sticky end, where unhybridized single DNA protrudes from the end of a double helix. The sticky end shown (ATCG) protrudes from double strandDNA (CACG on the bottom strand). Dna nanostructures John Relf, Thomas LeBean, DNA Nanotechnology and its Applications, chapter 13 in Bio-Inspired and Nano-scale Integrated Computing. Wiley, USA (2007) • Sticky ends are often used to combine two DNA nanostructures together via hybridization of their complementary single strand DNA. The Figure shows the antiparallel nature of double strand DNA with the 5’ end of each strand pointing toward the 3’ end of its partner strand.

24. DNA nanostructures have some unique advantages among nanostructures: • They are relatively easy to design • Fairly predictable in their geometric structures • And have been experimentally implemented in a growing number of labs around the world • They are constructed primarily of synthetic DNA • A key principle in the study of DNA nanostructures is the use of self-assembly processes to actuate the molecular assembly. Dna nanostructures John Relf, Thomas LeBean, DNA Nanotechnology and its Applications, chapter 13 in Bio-Inspired and Nano-scale Integrated Computing. Wiley, USA (2007)

25. There are a number of key challenges still confronting this emerging field on DNA nanostructures, including: • The need for error-correction • and the challenge and applications of constructing three dimensional DNA lattices. Future development

26. Overviewed were a number of methods for assembling computational patterns within the molecular fabric of DNA lattices. Surveyed were the varied interdisciplinary techniques for carefully designing and controlling these self assembly processes. Many of these self-assembly processes are computational based and programmable and it seems likely that interdisciplinary techniques will be essential to other emerging subfields of nanoscience and biomolecular computation. Conclusion #2

27. John Relf, Thomas LeBean, DNA Nanotechnology and its Applications, chapter 13 in Bio-Inspired and Nano-scale Integrated Computing. Wiley, USA (2007) Zhaoxiang Deng, Yi Chen, Ye Tian, Chengde Mao, A fresh look at DNA 40 nanotechnology, chapter in Nanotechnology: Science and Computation (eds. J.Chen; N. Jonoska & G. Rozenberg), Springer, pp 23-34, (2006). Nadrian C. Seeman, Nanotechnology and the Double Helix; Scientific American, 290 (6), 64-75 (June 2004). Paul W. K. Rothemund, Folding DNA to create nanoscale shapes andpatterns, Nature 440, 297-302 (16 March 2006). Work cited

28. S2Rebuttal: Applications of Genomics Please Prepare a Rebuttal (MISSING)

29. S1Rebuttal: Applications of Genomics Please Prepare a Rebuttal (MISSING)

30. By Group S3: Michael Koetting Bradford Lamb James Kancewick Review of S2—Nanotechnology in Genomics

31. Very good flow of information. Had a smooth transition between the introductory slides and the more detailed slides on the research. Consistent slide formatting makes for an aesthetically pleasing presentation. Captions explaining images are very useful in understanding the figures presented. The text is very detailed—perfect for a slideshow with no physical presentation. Conclusions of each paper’s discussion and identification of challenges were very helpful in understanding the level of progress made in the papers with respect to long-term goals. Things done well!

32. Too many slides without images. Images are necessary to help keep the audience entertained. Some of the images in the slideshow are too small to read easily. Larger images with text could be placed on their own slide to maximize the image size/readability. The “Conclusion #2” slide needs to be broken up into bullet points rather than being one paragraph. This would make it easier to read and would highlight the important points better. Furthermore, the “Conclusion #2” slide’s title seems out of place since there was never a slide titled “Conclusion #1.” All of the citations for images should be placed in the presentation. Areas for Improvement

33. S4 Review of S2 Danielle Miller Josh Moreno Scott Marwil

34. Things Done Well • Slides looked very professional. • Punctuation was fairly consistent, much better than most presentations. Slides 14, 24 and 25 had a couple inconsistencies. • Nice pictures. A lot of them were vibrant.

35. Things to Improve On • A lot of text. There are a bunch of long paragraphs on slides. Try to break concepts down for audience. • The shadow on the titles of the slides looks cool, but it is very distracting. • Make sure your titles fit within the area your slide design has designated for titles. Don’t let them cross the horizontal line.

36. Things to Improve On • Words and pictures overlapping. • Use consistent placement for your citations. • Slide 13 needs some work with regard to aesthetics. • Don’t capitalize ‘Figure’ unless it is part of a name (i.e. Figure 3). • Some words too small.

37. S5Rebuttal: Applications of Genomics Please Prepare a Rebuttal (MISSING)