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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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  • 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  

  • 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  

  • 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  

  • January 10, 2012
  • 07:00 PM
  • 1,332 views

Having kids wears you out? Same holds for telomeres. In zebra finches.

by EE Giorgi in CHIMERAS

One of my most popular posts on the blog has been The Immortality Paradox, in which I discuss telomeres, aging, and cancer. Telomeres are the ends of he chromosomes, a bit of non-coding DNA that naturally wears off as cells divide and as we age. Once the telomeres reach a certain critical length the cell stops dividing and eventually dies. As a consequence, telomeres length varies across age groups but, even within the same age group, it varies from individual to individual. So, it becomes natur........ Read more »

Heidinger, B., Blount, J., Boner, W., Griffiths, K., Metcalfe, N., & Monaghan, P. (2012) Telomere length in early life predicts lifespan. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1113306109  

  • January 9, 2012
  • 09:10 AM
  • 1,133 views

Chaperon proteins do more than... chaperon

by EE Giorgi in CHIMERAS

The full human genome was typed for the first time in 2003. Ever since, there has been a "hunt" for mutations and, more in general, associations between genotypes and phenotypes. As I have pointed out multiple times on this blog, things have turned out more complicated than originally anticipated: what happens between DNA and proteins (what we could consider the "end" product) is still very much a "black box" in which epigenetic changes and RNA editing can completely turn around the outcome. Fur........ Read more »

  • January 6, 2012
  • 08:56 AM
  • 1,445 views

The curse of drug-resistant TB strains

by EE Giorgi in CHIMERAS

Tuberculosis (TB) is a disease caused by a number of strains of mycobacteria. It affects mostly the lungs with chronic, bloody cough and fever. It can remain asymptomatic as a latent infection, though about 10% of these latent infections eventually progress to active disease.The two most common drugs used to treat TB are isoniazid and rifampicin, but unfortunately new mycobacteria strains (called MDR strains, which stands for multi-drug resistant) have emerged that are resistant to both these po........ Read more »

  • January 3, 2012
  • 09:06 AM
  • 1,296 views

A lot happens in the blink of an eye!

by EE Giorgi in CHIMERAS

Do you have recurrent nightmares? I do, especially when I'm under a lot of stress. I often dream of missing a train. The setting, location, company and place I need to reach change every time, but the common factor is always the frightening sense of having missed the train and not being able to make it. Another recurrent nightmare I have is that the light is so bright I can't keep my eyes open. So I start blinking faster and faster but I can't see a thing and end up missing something very import........ Read more »

Bristow, D., Haynes, J., Sylvester, R., Frith, C., & Rees, G. (2005) Blinking Suppresses the Neural Response to Unchanging Retinal Stimulation. Current Biology, 15(14), 1296-1300. DOI: 10.1016/j.cub.2005.06.025  

Bonfiglio L, Sello S, Carboncini MC, Arrighi P, Andre P, & Rossi B. (2011) Reciprocal dynamics of EEG alpha and delta oscillations during spontaneous blinking at rest: a survey on a default mode-based visuo-spatial awareness. International journal of psychophysiology : official journal of the International Organization of Psychophysiology, 80(1), 44-53. PMID: 21238505  

  • December 29, 2011
  • 10:02 AM
  • 1,346 views

Beta blockers and genetic variation

by EE Giorgi in CHIMERAS

It's happening again.I'm sitting in a meeting, and suddenly I feel my hands prickling. My heart thumps faster. I can't concentrate on what people around me are saying. My head is buzzing, and cold sweat trickles down my neck. I feel the tingling of panic biting at the tip of my fingers. My muscles tense, adrenaline spikes. Every cell of my body screams, "Danger!"Now, part of me wants to take out my notebook and jot everything down for my next high-adrenaline, action-packed story.The other (more ........ Read more »

  • December 26, 2011
  • 10:19 AM
  • 1,358 views

Sense and antisense in the human genome

by EE Giorgi in CHIMERAS

I hope you all had a wonderful holiday. Short post today, as I'm sure we're all still digesting all the yummy holiday food and sweets, and maybe some of you are still celebrating. One of my recurrent topics on the blog has been antisense genes. Until recently, I had no idea such things existed, let alone in humans. It turns out, they are quite abundant in humans. Antisense genes are overlapping genes that are transcribed on opposite DNA strands. I've discussed how antisense genes regulate conjug........ Read more »

He, Y., Vogelstein, B., Velculescu, V., Papadopoulos, N., & Kinzler, K. (2008) The Antisense Transcriptomes of Human Cells. Science, 322(5909), 1855-1857. DOI: 10.1126/science.1163853  

  • December 22, 2011
  • 08:22 AM
  • 1,423 views

Guest post: How to camouflage a virus and why it's important

by EE Giorgi in CHIMERAS

Last week I covered a couple of recent gene therapy studies and discussed the different types of vectors used in order to make these therapies more efficient. One of the obstacles that hinders the efficiency of gene therapy is the immune system: if the patient has previously developed immunity against the viral vector, the virus will be quickly cleared out of the system without being able to deliver the genes. Therefore, the question is: how can we prevent the immune system from attacking the vi........ Read more »

  • December 20, 2011
  • 08:21 AM
  • 1,382 views

Fingerprint evidence: not exactly what CSI showed you

by EE Giorgi in CHIMERAS

Every scientific type of analysis has an error rate. I've mentioned it before: science is not about certainty, it's about accurately measuring the uncertainties. Unfortunately, when it comes to forensic sciences, this causes a logical problem: scientists like to talk about being 90% sure about something, but in trials there's only two outcomes: innocent or guilty. You can't do 90% guilty and 10% innocent.It occurred to me that this was an issue when I heard somebody talk about how fingerprint an........ Read more »

  • December 18, 2011
  • 10:07 AM
  • 1,593 views

Enough with OXTR associations. Here's what I really want to know.

by EE Giorgi in CHIMERAS

Another OXTR paper came out in PNAS, the third since September. Apparently people are finding more and more association between a common OXTR polymorphism, rs53576, and various behaviors: "One SNP in the third intron of OXTR has emerged as a particularly promising candidate in recent studies on human social behavior: rs53576 (G/A). In recent studies, the A allele of rs53576 has been associated with reduced maternal sensitivity to child behavior, lower empathy, reduced reward dependence, lower op........ Read more »

Chen, F., Kumsta, R., von Dawans, B., Monakhov, M., Ebstein, R., & Heinrichs, M. (2011) Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans. Proceedings of the National Academy of Sciences, 108(50), 19937-19942. DOI: 10.1073/pnas.1113079108  

  • December 17, 2011
  • 09:49 AM
  • 1,562 views

Epigenetic reprogramming: how cells start afresh

by EE Giorgi in CHIMERAS

Last week I talked about the chromatin, the complex of DNA and proteins that resides inside the nucleus. There were two key points to that post: (1) the topology inside of the chromatin, or, in other words, how the chromosomes are arranged inside the nucleus, is correlated to which genes are active and which aren't; (2) these changes in the chromatin that allow for gene expression and gene silencing can be inherited, though how it's still a mystery.I admit I left that second point a bit vague la........ Read more »

Smallwood SA, & Kelsey G. (2011) De novo DNA methylation: a germ cell perspective. Trends in genetics : TIG. PMID: 22019337  

  • 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 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 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  

  • December 9, 2011
  • 10:04 AM
  • 1,562 views

Understanding the cell nucleus in order to unravel the mystery of epigenetic heritability

by EE Giorgi in CHIMERAS

The above image is the striking view of the surface of a cell nucleus (in pink). The dark crater represents a hole in the nucleus and offers a peek inside: the granular consistency that you see there are the chromosomes, bundled together in what may appear a random distribution but, in reality, is nothing but random:"In all eukaryotic species analyzed so far, spatial genome arrangements are nonrandom: chromosomes or genomic loci occupy preferential positions with respect to each other and/or to ........ Read more »

  • December 8, 2011
  • 08:14 AM
  • 1,203 views

Timing the AIDS pandemic and why it made history (Part II)

by EE Giorgi in CHIMERAS

In Part I of this post I discussed the Science paper that proved HIV was the result of a cross-transmission from chimpanzees to humans. In that paper, Hahn et al. conclude with an open question: "The timing of SIVcpz transmission to humans, leading ultimately to the HIV-1 pandemic, has been a challenging question. We know from analyses of stored samples that humans in west central Africa had been infected with HIV-1 group M viruses by 1959 and with group O viruses by 1963. But how much earlier w........ Read more »

B. Korber, M. Muldoon, J. Theiler, F. Gao, R. Gupta, A. Lapedes, B. H. Hahn, S. Wolinsky, and T. Bhattacharya. (2000) Timing the Ancestor of the HIV-1 Pandemic Strains. Science, 288(5472), 1789-1796. DOI: 10.1126/science.288.5472.1789  

  • 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  

  • 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 »

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