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A mathematician by training, I discovered genetics in 2006 and never turned back. This blog was born to share all the fascinating things I learn about genes and DNA through my current research on viral genetics and HIV.

EE Giorgi
188 posts

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  • December 13, 2011
  • 02:10 PM
  • 5,190 views

Not all vectors are created equal

by EE Giorgi in CHIMERAS

As I was reading the paper I discussed yesterday, I realized there was a part I didn't fully understand and I needed to research more. I received some great comments on that post that pointed me in the right direction.A gene delivery vector is an engineered virus modified so that it contains the genes needed for therapy. Once inside the cell, the genetic material needs to reach the nucleus where it has to recruit a complementary DNA strand in order for the gene to be expressed. Conceptually, it ........ Read more »

  • December 15, 2011
  • 08:43 AM
  • 4,993 views

So mice can be vaccinated against HIV. What about humans, though?

by EE Giorgi in CHIMERAS

I hope I can get away with yet another paper on gene therapy this week. You may actually have already heard about this one: it came out at the end of November and it had quite some resonance because the researchers claimed to have establish lasting immunogenicity to HIV in mice‚ using, again gene therapy. I have already discussed the potential use of gene therapy to cure HIV. In fact, the only human to ever be "cured" of HIV was a leukemia patient who, after receiving a genetically modified ve........ Read more »

  • December 12, 2011
  • 07:16 PM
  • 4,941 views

Another gene therapy success story

by EE Giorgi in CHIMERAS

Last October I reported an incredible story in which researchers used an HIV chimeric virus to cure leukemia. Here's another success story. Hemophilia B is a blood clotting disorder caused by spontaneous mutations in the Factor IX gene, leading to a deficiency of Factor IX, an enzyme essential in blood coagulation. The gene is expressed mostly in the liver, where the enzyme is produced and then sent into circulation in the blood. Less than 1% of normal levels of Factor IX lead to severe hemophil........ Read more »

Nathwani, A., Tuddenham, E., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D., Chowdary, P., Riddell, A., Pie, A., Harrington, C.... (2011) Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B. New England Journal of Medicine, 2147483647. DOI: 10.1056/NEJMoa1108046  

  • November 29, 2011
  • 08:41 AM
  • 2,285 views

Sample size, P-values, and publication bias: the positive aspects of negative thinking

by EE Giorgi in CHIMERAS

If you follow the science blogging community, you may have noticed a lot of talking about sample size in the past couple of weeks. So I did my share of mulling things over and this is what I came up with.1- The study in question had a small sample size but reported a significant p-value (<0.05). Such study is NOT underpowered. An underpowered study is a study that does not have a sufficiently large sample size to allow detection of a significant result. A significant result is by definition a........ Read more »

  • December 2, 2011
  • 09:40 AM
  • 2,208 views

Another genetic puzzle: why is mitochondrial DNA only inherited through the mother's side?

by EE Giorgi in CHIMERAS

Remember when I told you that bacteria have circular DNA? Well, we have it too, only not in the nucleus where the rest of our DNA sits. It's a rather interesting story, one that biologist Lynn Margulis proved in 1967 [1]: our cells contain organelles called mitochondria, which originally were separate organisms (prokaryotes), and at some point entered a symbiotic relationship with eukaryotic cells through endosymbiosis. As a result, they contain their own, circular DNA called mitochondrial DNA o........ Read more »

  • January 13, 2012
  • 08:51 AM
  • 2,159 views

Sickle cell anemia, malaria, and the heterozygote advantage

by EE Giorgi in CHIMERAS

Hemoglobin is the oxygen-carrying protein found in the red cells of our blood. Patients with sickle cell anemia have a sickle form of hemoglobin. While healthy red cells are shaped like a disk pinched in the middle (a doughnut without a whole), in patients affected by the disease the sickle hemoglobin forms strands which cause the red cells to be shaped like a crescent. This causes all sorts of complications and risks: the sickle red cells are more rigid and increase the risk of ischemia and nec........ Read more »

Salih NA, Hussain AA, Almugtaba IA, Elzein AM, Elhassan IM, Khalil EA, Ishag HB, Mohammed HS, Kwiatkowski D, & Ibrahim ME. (2010) Loss of balancing selection in the betaS globin locus. BMC medical genetics, 21. PMID: 20128890  

  • September 30, 2011
  • 08:02 PM
  • 2,038 views

Deep sequencing and forensic science: how to improve DNA fingerprinting

by EE Giorgi in CHIMERAS

(In case you missed it, this originally appeared last Thursday as a guest blog on the Writer's Forensics Blog.)There are roughly three billion pairs of nucleotides in human DNA, and the vast majority is identical across individuals. When we talk about “genetic fingerprinting,” we really mean, “looking for a needle in a hay stack.” Luckily, for the most part, we all differ at the same loci. Over the years, the techniques used for DNA typing have improved greatly, diminishing both costs an........ Read more »

Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, Berka J, Braverman MS, Chen YJ, Chen Z.... (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature, 437(7057), 376-80. PMID: 16056220  

Fordyce SL, Ávila-Arcos MC, Rockenbauer E, Børsting C, Frank-Hansen R, Petersen FT, Willerslev E, Hansen AJ, Morling N, & Gilbert MT. (2011) High-throughput sequencing of core STR loci for forensic genetic investigations using the Roche Genome Sequencer FLX platform. BioTechniques, 51(2), 127-33. PMID: 21806557  

  • September 11, 2011
  • 11:46 AM
  • 1,968 views

How did that pesky virus end up in our DNA?

by EE Giorgi in CHIMERAS

Last time we talked about the different types of genetic and epigenetic chimeras. We learned what a chimeric virus is, and that retroviruses need to get integrated into the host's DNA in order to replicate. They basically inject their RNA into the cell, the RNA gets transformed into DNA, the viral DNA enters the cell's nucleus and once in the the nucleus it's integrated into the cell's DNA.This process has been going on for as long as viruses have existed. And viruses have existed for a long tim........ Read more »

Dunlap KA, Palmarini M, Varela M, Burghardt RC, Hayashi K, Farmer JL, & Spencer TE. (2006) Endogenous retroviruses regulate periimplantation placental growth and differentiation. Proceedings of the National Academy of Sciences of the United States of America, 103(39), 14390-5. PMID: 16980413  

  • January 17, 2012
  • 09:06 AM
  • 1,930 views

Introns, exons, and stop codons: how antisense oligonucleotides can fix frameshift mutations

by EE Giorgi in CHIMERAS

DMD is the largest gene in nature, covering roughly 2.4 mega bases of the X chromosome. It encodes the dystrophin protein, a component of the protein complex that connects the cytoskeleton to the extra-cellular matrix. DMD is a very complex gene. Its RNA transcripts are differentially spliced, which means that the gene produces different transcripts, encoding a large set of protein isoforms. A refresher: every gene is composed of coding parts, called exons, interspersed with non-coding bits, cal........ Read more »

Goemans, N., Tulinius, M., van den Akker, J., Burm, B., Ekhart, P., Heuvelmans, N., Holling, T., Janson, A., Platenburg, G., Sipkens, J.... (2011) Systemic Administration of PRO051 in Duchenne's Muscular Dystrophy. New England Journal of Medicine, 364(16), 1513-1522. DOI: 10.1056/NEJMoa1011367  

  • May 11, 2012
  • 08:20 AM
  • 1,896 views

Flat tori in 3D

by EE Giorgi in CHIMERAS

It's been a while since I've read a pure math paper, but when I saw the picture I knew I had to pick this one up. For the pure mathematicians out there: I haven't done pure math since my grad years, so feel free to pitch in and correct me if I misunderstood any of the following! "Torus" is mathematics for donut. Take a very flexible square -- imagine it's made of rubber -- roll it, then glue together the circles at the two ends. Congratulations. You've made a torus. Now suppose you live on the........ Read more »

Borrelli, V., Jabrane, S., Lazarus, F., & Thibert, B. (2012) From the Cover: Flat tori in three-dimensional space and convex integration. Proceedings of the National Academy of Sciences, 109(19), 7218-7223. DOI: 10.1073/pnas.1118478109  

  • November 30, 1999
  • 12:00 AM
  • 1,867 views

More on the viruses inside us: retrotransposons

by EE Giorgi in CHIMERAS

Retrotransposons... Read more »

  • February 21, 2012
  • 08:15 AM
  • 1,718 views

Is cancer contagious? Sometimes. But it may not be bad thing.

by EE Giorgi in CHIMERAS

About 15% of all cancers worldwide are caused by infectious pathogens such as viruses, bacteria, or parasites [1]. Viruses that are capable of inducing cancer are called oncoviruses -- HPV is an example. The pathogen is transmitted from a donor to a recipient, starts the infection, and the infection eventually causes the cancer. But did you know there existed such a thing as a transmissible cancer? In this case, it's not the pathogen, but the cancer cell line itself that gets transmitted from on........ Read more »

Welsh, J. (2011) Contagious Cancer. The Oncologist, 16(1), 1-4. DOI: 10.1634/theoncologist.2010-0301  

Rebbeck, C., Leroi, A., & Burt, A. (2011) Mitochondrial Capture by a Transmissible Cancer. Science, 331(6015), 303-303. DOI: 10.1126/science.1197696  

  • November 26, 2011
  • 09:50 AM
  • 1,716 views

I know that face! Sort of...

by EE Giorgi in CHIMERAS

In graduate school I had a Chinese friend who one day asked me the name of the fellow student who'd just stopped by to borrow a book. I told her, she thanked me, and added, "It's so hard for me to remember faces. You guys look all alike to me."Now, you have to understand that I'm petite, brunette with dark eyes (very Italian), and the girl she'd just asked about was the typical Northern European type, tall, blond, and blue eyes. The concept was truly intriguing. I tend to mix up Eastern A........ Read more »

  • August 17, 2014
  • 11:26 AM
  • 1,700 views

A mosaic vaccine that could potentially protect from different ebola strains

by EE Giorgi in CHIMERAS

Disclaimer: The mosaic vaccine paper discussed in this article is from my own group and overlaps with some of the research I do. I'm sure you've been following the latest news about the Ebola virus outbreak in Africa."The Ebola outbreak in West Africa is the world's deadliest to date and the World Health Organization has declared an international health emergency as more than 1,000 people have died of the virus in Guinea, Liberia, Sierra Leone and Nigeria this year." [Source: BBC News]The e........ Read more »

Friedrich BM, Trefry JC, Biggins JE, Hensley LE, Honko AN, Smith DR, & Olinger GG. (2012) Potential vaccines and post-exposure treatments for filovirus infections. Viruses, 4(9), 1619-50. PMID: 23170176  

Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD.... (2007) Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nature medicine, 13(1), 100-6. PMID: 17187074  

  • September 18, 2011
  • 09:33 AM
  • 1,691 views

Is an HIV vaccine finally possible? Unraveling the secrets of broadly neutralizing antibodies

by EE Giorgi in CHIMERAS

Last month I talked about the daunting challenge that HIV has presented for the past thirty years. HIV is so variable that as soon as the immune system builds a defense against it, the virus comes up with a new variant that allows it to escape. The only way to defeat such an elusive enemy is with immune responses able to recognize a broad range of HIV subtypes and variants. Unfortunately, antibodies with these characteristics are produced by a minority of patients and only years into the infecti........ Read more »

Wu, X., Zhou, T., Zhu, J., Zhang, B., Georgiev, I., Wang, C., Chen, X., Longo, N., Louder, M., McKee, K.... (2011) Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049), 1593-1602. DOI: 10.1126/science.1207532  

Scheid, J., Mouquet, H., Ueberheide, B., Diskin, R., Klein, F., Oliveira, T., Pietzsch, J., Fenyo, D., Abadir, A., Velinzon, K.... (2011) Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. Science, 333(6049), 1633-1637. DOI: 10.1126/science.1207227  

  • October 4, 2011
  • 06:51 AM
  • 1,663 views

Gene therapy makes sense. And antisense, too!

by EE Giorgi in CHIMERAS

Genes code proteins. When a gene carries a defective mutation, it will either stop coding the protein or it will code a defective one. This is, unfortunately, the basis of many genetic diseases. In principle, if we could substitute the defective gene with a healthy one, the problem would be solved. That's what gene therapy boils down to. In fact, there are ways to deliver the genes to the affected cells. For example, you can take a virus that targets the cells where the defective gene is express........ Read more »

Suto, R., Tominaga, K., Mizuguchi, H., Sasaki, E., Higuchi, K., Kim, S., Iwao, H., & Arakawa, T. (2004) Dominant-negative mutant of c-Jun gene transfer: a novel therapeutic strategy for colorectal cancer. Gene Therapy, 11(2), 187-193. DOI: 10.1038/sj.gt.3302158  

Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP.... (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science (New York, N.Y.), 314(5796), 126-9. PMID: 16946036  

Zhang Y, Zhu C, & Pardridge WM. (2002) Antisense gene therapy of brain cancer with an artificial virus gene delivery system. Molecular therapy : the journal of the American Society of Gene Therapy, 6(1), 67-72. PMID: 12095305  

  • January 18, 2012
  • 11:14 PM
  • 1,649 views

Regenerating tissue through autologous cells: a personal appeal

by EE Giorgi in CHIMERAS

The trachea is one of the most challenging organs to transplant, with a high risk of necrosis and infection due to inadequate graft revascularization and the fact that it's constantly exposed to airborne elements. Transplants requires lifelong immunosuppression, which also carry high risks. Prosthesis can rupture, generate infection, and cause injury. What to do then? One answer is tissue engineering.Dr. Paolo Macchiarini is one of the pioneers in this techniques. In a recent paper [1] he and hi........ Read more »

Jungebluth, P., Moll, G., Baiguera, S., & Macchiarini, P. (2011) Tissue-Engineered Airway: A Regenerative Solution. Clinical Pharmacology , 91(1), 81-93. DOI: 10.1038/clpt.2011.270  

  • September 26, 2011
  • 08:36 AM
  • 1,629 views

Overlapping genes, nested genes, and antisense genes: how complex can genomes be?

by EE Giorgi in CHIMERAS

HIV has 10 genes spread throughout roughly 10 thousand nucleotides. The genes Rev and Tat (and Tev, when it’s present), completely overlap with the larger gene Env. When a gene lies within another, we say that the two genes are “nested.” How does the virus know which protein to code if the information is overlapping? The key is the “reading frame.” Remember, a gene is a string of nucleotides (A, G, C, and T), and a protein is a string of amino acids (also denoted with letters), so it r........ Read more »

Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP, & Cui H. (2008) Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature, 451(7175), 202-6. PMID: 18185590  

Guo JH, Cheng HP, Yu L, & Zhao S. (2006) Natural antisense transcripts of Alzheimer's disease associated genes. DNA sequence : the journal of DNA sequencing and mapping, 17(2), 170-3. PMID: 17076261  

Chatterjee A, Johnson CM, Shu CC, Kaznessis YN, Ramkrishna D, Dunny GM, & Hu WS. (2011) Convergent transcription confers a bistable switch in Enterococcus faecalis conjugation. Proceedings of the National Academy of Sciences of the United States of America, 108(23), 9721-6. PMID: 21606359  

  • February 13, 2012
  • 08:05 AM
  • 1,609 views

The "not-so-universal" genetic code, its origin and its evolution

by EE Giorgi in CHIMERAS

From [1]:"Until relatively recently, the [genetic] code was thought to be invariable, frozen, in all organisms, because of the way in which any change would produce widespread alteration in the amino acid sequences of proteins. The universality of the genetic code was first challenged in 1979, when mammalian mitochondria were found to use a code that deviated somewhat from the universal."A brief refresher: proteins are chains of amino acids. They are made from messenger RNA by assigning each tri........ Read more »

Ohama T, Inagaki Y, Bessho Y, & Osawa S. (2008) Evolving genetic code. Proceedings of the Japan Academy. Series B, Physical and biological sciences, 84(2), 58-74. PMID: 18941287  

  • December 5, 2011
  • 09:12 AM
  • 1,598 views

Timing the AIDS pandemic and why it made history (part I)

by EE Giorgi in CHIMERAS

This week I would like to discuss two Science papers that have marked a milestone in HIV research. In order to place them in the right context, I need to start with a brief historical digression. If you're interested in the history of the discovery of the AIDS disease, I highly recommend watching the movie And the Band Played On. It's very well done and realistically portrays how the medical investigation was conducted. For the purpose of my discussion here, though, I will start from the movemen........ Read more »

Hahn, B., Shaw, G. M., De Cock, K. M, Sharp, P. M. (2000) AIDS as a Zoonosis: Scientific and Public Health Implications. Science, 287(5453), 607-614. DOI: 10.1126/science.287.5453.607  

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