Gene Editing and CRISPR

Pre-approved Topic List

1. How do CRISPR systems work on the molecular level? What was their original purpose? How did they evolve?
2. Why are CRISPR systems useful for modern genome engineering? How do they compare to other techniques such as zinc fingers?
3. CRISPR-based techniques rely on protein such as Cas12 or Cas9. Are some of the properties of these proteins undesirable? How might we engineer these proteins to work better?
4. On a molecular level, what components in living organisms are used to implement the specific genetic code that exists? How can we modify these components to create new genetic codes? What benefits would different genetic codes have for engineering purposes?
5. What are recent developments in the field of CRISPR, such as CRISPR-guided base editors and prime editing?
6. How can CRISPR systems be used to modify the genomes of entire wild populations using ‘gene drive’ constructs? What are possible applications of gene drives? What are the technical challenges to implementing gene drives safely? What are the ethical implications of using gene drives?
7. Large-scale engineering projects require project management strategies. In biological engineering, what are good strategies for assessing the quality and feasibility of an idea? How should one go about rapidly de-risking and implementing a new engineering approach?
8. When our engineering goals require biomolecules with functions not found in nature, we can attempt to create these new components with rational or computational design approaches, with directed evolution, or both. How do these protein engineering techniques work? How do we assess which approach is likely to be successful in a particular situation?
9. How did life originate? How did the divide between genetic material (DNA) and functional biomolecules (proteins) come to exist? How did the genetic code come to exist?
10. Why is the universally conserved genetic code structured the way it is? In particular, why does it use three-base codons, why are the codons assigned to specific amino acids, why do some amino acids have more codons, and why were the specific 20 amino acids chosen?
11. What can directed evolution experiments teach us about how evolution works? Conversely, can evolution research of organisms in the wild guide best practices for directed evolution experiments in the laboratory?
12. If we want to add a new amino acid to the genetic code, or rearrange which codon encodes which amino acid, what engineering approaches are available to us? What are the strengths and weaknesses of these different approaches?
13. What inspiration can we take from computer science that may help us engineer biological systems? Do concepts like logic gates and abstraction exist in biology, and if not, how do we implement them?
14. Proteins are chemically complex, enabling proteins to perform diverse chemical functions in the cell, but be difficult to engineer and model. In contrast, DNA less chemically complex. How can we exploit the simplicity of DNA’s chemical structure to predict the shape that a strand of DNA will adopt? How do we use this predictive capability to engineer custom DNA shapes (like smiley faces), or processes (like an AND logic gate)? What are the limits of DNA nanotechnology?
15. CRISPR enzymes can have off-target effects that may have unintended side effects of a therapy. What are strategies that are used to identify these off-target effects. How are these off-targets avoided and how are CRISPR enzymes engineered to alleviate this problem?
16. Some CRISPR systems don’t act on DNA but, instead, on RNA. What function do these proteins have and how are these interesting proteins being harnessed for treating human disease?
17. How can CRISPR systems be used to treat human disease outside of gene editing? How are CRISPR proteins being used to change the expression of genes and why would one want to do this?
18. If you wanted to insert an entirely new gene into the genome, how would you achieve this? What current technologies are used for gene insertion, what are their limitations, and what new technologies on the horizon can transform this problem?
19. How are CRISPR enzymes being used to treat humans today? What kinds of diseases are being treated, why were they chosen, and how are CRISPR enzymes critical to the success of the treatment? What are the limitations of CRISPR in the clinic that have limited its ability to treat more diseases?
20. If you wanted to treat a genetic disease in a living human with CRISPR, how would you get the enzyme to the diseased tissue of interest? How and why are viruses commonly used to deliver CRISPR to cells?
21. How can CRISPR enzymes be used to diagnose disease? SHERLOCK and DETECTR are two platforms for detection of diseases and viruses. What are these tools, why are they increasingly gaining popularity as diagnostics, and how are these platforms being applied to detect viruses like COVID-19?
22. New CRISPR enzymes are found every day from nature using computational tools. What are these computational tools, how do they work, and what new enzymes have been found using these techniques?
23. Next-generation sequencing is a transformative technology used by companies like 23andMe and Ancestry.com, by enabling rapid and inexpensive reading of DNA. How does next-generation sequencing work and how is it applied in research and in the clinic?
24. Is it ethically appropriate to modify genomes including humans? What are the risks and how can we foresee the potential outcomes?
25. How can we use online genetic data in order to study genetic diseases and roles of genes in cell biology?
26. Why is DNA sequencing important for scientific research? How does next generation sequencing compare with the previous sequencing methods, such as Sanger sequencing? And how are they simultaneously used in research?
27. How has the next generation sequencing transformed scientific research? What is the 1000 genome and 100,000 genome projects?
28. Most testing for COVID-19 is currently done on viral genetic material from nose and throat swabs, using reverse transcription polymerase chain reaction (RT-PCR). The next big goal is to develop a serological test. What are the molecular principles qPCR and PCR. What might be the issues associated with this diagnostic technique?
29. All cancers arise as a result of changes that have occurred in the DNA sequence of the genomes of cancer cells, but not all mutations in cancer cells are involved in the development of cancer. What are driver and passenger mutations and why is it important to differentiate between them? How is the cancer genetic research revolutionizing treatment and management of cancer patients (with regards to cancer in general or a specific cancer type)?
30. Some RNA molecules fold into well-ordered structures. Given RNA sequences, how can these structures be predicted computationally? Are there useful applications for “riboswitches” which change their folds in response to a molecular signal?
31. How is epigenetic information written and read during the life cycles of cells and organisms? What kinds of epigenetic information are transferred between generations? How can CRISPR technology be used to alter the epigenome?
32. Why are stem cells special? What different kinds of stem cells are there? How can stem cells be used in research and therapeutics?
33. What are the various ways CRISPR systems are used to dissect fundamental biology and understand the function of genes?
34. Can CRISPR be used to help edit RNA? What are the applications and benefits of RNA editing?
35. What are the various ways CRISPR is being used as a diagnostic, and what are the benefits of CRISPR based diagnostics?
36. Is gene therapy the future of cancer treatment and prevention? If so, how do we best deliver it?
37. How can we unlock the potential of RNAs to treat disease? From MicroRNA to messanger RNA.
38. Viral or non-viral, that is the question-which is best for gene therapy and why?
39. Therapeutic Potential of Stem Cells: How can stem cells be used in regenerative medicine to repair damaged tissues and organs?
40. Stem Cells in Disease Modelling: How do scientists use stem cells to model diseases in the laboratory? How are stem cells being used to study and potentially treat genetic disorders? What insights have stem cells provided in understanding complex diseases like cardiovascular diseases?
41. Stem Cells in Cardiovascular Repair: How are stem cells contributing to advancements in cardiovascular medicine, particularly in heart regeneration? What are the successes and limitations seen in recent research?
42. Ethical and Regulatory Aspects: What are the key ethical concerns and regulatory challenges associated with stem cell research? How do these issues impact the development and application of stem cell therapies?

Additional Topics in Genomics:

1. What are the limitations of genome-wide association studies (GWAS)? Given these limitations, how can we still use them to understand and treat disease?
2. How does the body use the same set of genes to produce cells with very different behavior, appearance and function?
3. What are the different kinds of ways a gene’s expression can be regulated? What are the advantages and disadvantages of each for an organism or a cell?
4. Gene imprinting: Why are ligers (the offspring of a male lion and a female tiger) much larger than lions OR tigers? Why are tigons (the reverse, an offspring of a female lion and a male tiger) much smaller?
5. How do our cells use ancient virus remnants to regulate gene expression?
6. How useful are the medical data you get when you do 23AndMe?
7. What are the ethical implications of services like 23AndMe? How should we protect genetic privacy? What protections already exist for personal genetic data?
8. Why is race a bad proxy for genetically-inherited risk for certain diseases?
9. What is the difference between self-reported race and genetic ancestry?
10. How can we use bioinformatic tools to understand genetic mutations and their affect in cells?
11. How can CRISPR be used to create patient-specific disease models and design targeted therapies for individuals with genetic disorders?
12. Bioinformatics in Pathogen Genome Sequencing: Use bioinformatics tools to analyse the genomes of various pathogens from animal sources, looking for genetic markers of disease transmission or resistance.
13. Comparative Genomic Studies for Animal-Derived Pathogens: Compare the genomes of pathogens isolated from animals with those from human infections to determine the evolution of virulence and resistance traits.
14. Using Bioinformatics to Decode Bacterial Genomic Adaptations: Employ bioinformatics tools to understand how bacteria adapt their genomes in response to different environments.
15. Impact of Bioinformatics on Vaccine Development Against Bacterial Pathogens : Examine how bioinformatics aids in identifying targets for vaccine development through genomic analysis.
16. Machine Learning and AI in Predicting Bacterial Infection Outcomes: Analyse the role of machine learning and AI in predicting the outcomes of bacterial infections, supported by bioinformatics.
17. How does bioinformatics enable the interpretation of vast amounts of data generated by next-generation sequencing? How can bioinformatics be utilized in uncovering biological foundations?
18. How has next-generation sequencing revolutionized our understanding of genetics and molecular biology, and what are its major applications and implications in areas such as medical diagnostics, evolutionary biology, and personalized medicine?
19. Fundamentals of Single Cell Sequencing: What is single cell sequencing and how does it differ from traditional bulk sequencing methods? What unique insights can we gain about cellular heterogeneity and function?
20. Single Cell Analysis in Embryonic Development: How is single cell sequencing transforming our understanding of early embryonic development? What can it reveal about the formation of different cell types and organogenesis?
21. Integrating Single Cell Data with Other Omics: How can single cell sequencing data be integrated with other omics data (like genomics, proteomics) to provide a more comprehensive view of cellular function and disease states?
22. What is enzyme replacement therapy? How can it be used to treat rare genetic diseases?