Philadelphia Chromosome

Philadelphia Chromosome

This illustration was created for JAAPA, February 2013 • 26(2).

The Philadelphia chromosome is formed when a piece of chromosome 9 exchanges places with a piece of chromosome 22, resulting in a balanced translocation t(9;22)(q34;q11) and the formation of an abnormal fusion gene BCR-ABL1.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. The American Cancer Society estimated that in 2012, the number of newly diagnosed CML cases would be 5,430, with 610 deaths.1 The discovery of the tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment and prognosis of CML, making imperative early recognition of CML. Timely diagnosis will ensure that patients receive early treatment, significantly improving their prognosis.

CML is caused by a cytogenetic abnormality that is thought to be acquired and involves a balanced translocation between chromosome 9 and chromosome 22. The BCR gene on chromosome 22 fuses with the ABL1 gene on chromosome 9, resulting in the abnormal fusion gene BCR-ABL1 located on chromosome 22 (Figure 1). The fusion gene produces a protein with tyrosine kinase activity that causes cells to proliferate. The resultant abnormal chromosome 22 [t(9;22)(q34;q11)] is also known as the Philadelphia (Ph) chromosome. It is identified in 95% of patients with CML and can be detected in all myeloid cells, including granulocytes, erythrocytes, monocytes, and B lymphocytes

Snip Vs. Shred

Snip Vs. Shred

Snip Vs. Shred

Project Description

By Alexander Gelfand, for the Johns Hopkins School of Public Health Magazine.
© Johns Hopkins University

The powerful genome-editing technology known as CRISPR-Cas made headlines this year—partly because many leading biologists called for a moratorium last March against using it to modify the genomes of human embryos, only to discover in April that Chinese scientists had already done just that.

But CRISPR-Cas is more than a genetic engineering tool with profound ethical implications. In fact, the tool itself is a modified version of one of several types of naturally occurring bacterial immune systems that fight the viruses known as bacteriophages. The particular system that researchers have adapted for gene-editing is a relatively rare and simple one called CRISPR-Cas9. Scott Bailey, PhD, Associate Professor in the Department of Biochemistry and Molecular Biology, recently described the atomic structure of a far more common, and far more complicated, CRISPR-Cas system called CRISPR-Cascade—one with profound implications of its own.

Bacteria use CRISPR-Cas systems to store the genetic signatures of phages that have previously infected them. These viral mugshots appear as stretches of DNA separated by short, repeated sequences. Together, the viral DNA and the repeats form arrays called clustered, regularly interspaced, short palindromic repeats, or CRISPRs. When a phage invades, CRISPR-Cas uses short strings of RNA to compare the phage’s DNA with its archive of viral signatures. If it finds a match, specialized CRISPR-associated (Cas) proteins are dispatched to disable the invader through various means. Those means depend on the particular flavor of CRISPR-Cas system involved: The Cas9 protein cuts neatly through phage DNA like a pair of molecular scissors; Cas3, employed by CRISPR-Cascade, chews it up like a shredder.

Using synthetic RNA, scientists can program CRISPR-Cas9 to target specific genes, allowing them to disrupt, delete, or replace DNA more quickly, easily, and cheaply than ever before. And whereas making changes to multiple genes at the same time was once extremely difficult and inefficient, CRISPR-Cas9 makes it simple. Its reliability and ease of use have already revolutionized genomic research, and could one day lead to clinical applications such as gene therapy.

Bailey, meanwhile, says that understanding how CRISPR-Cascade fends off phages could help scientists design microbes that are super-resistant to viruses. That would be a boon the pharmaceutical industry, which uses genetically engineered bacteria and yeast to produce a variety of drugs, including insulin. Learning Cascade’s secrets could also help scientists weaken the bacterial immune system in order to kill harmful microbes, better understand (and therefore prevent) antibiotic resistance—and ultimately generate new ways of grappling with bacteria that researchers have not yet even begun to imagine.

The CRISPR-Cas system was discovered by dairy-industry researchers who wanted to stop phages from ruining the bacterial cultures that are used to make cheese and yogurt.

CRISPR-Cas9 has worked everywhere it has been applied—from wheat and trees to monkeys and mice. In laboratory experiments on human cells, researchers have used it to remove HIV DNA from a human genome and to fix a mutation that causes cystic fibrosis.

Cascade stands for “CRISPR-associated complex for antiviral defense.” Bailey and doctoral student Sabin Mulepati visualized CRISPR-Cascade’s large, complex structure using a technique called x-ray crystallography—and a particle accelerator housed at Stanford University.

Acknowledgements: Sourceforge Qutemol

Project Details

Client Johns Hopkins Bloomberg School of Public Health
Date 2015
Skills Editorial, Molecular, CRISPR-Cas9/Cas3
Media PyMol, Adobe Photoshop, Adobe Illustrator

Project Feature

Layout for printed full-page magazine spread.

Project Feature

Simplified infographic layout for online web article



Bacteriorhodopsin is a protein used by Archaea, the most notable one being Halobacteria. It acts as a proton pump; that is, it captures light energy and uses it to move protons across the membrane out of the cell.[1] The resulting proton gradient is subsequently converted into chemical energy.[2]

Bacteriorhodopsin is an integral membrane protein usually found in two-dimensional crystalline patches known as “purple membrane”, which can occupy up to nearly 50% of the surface area of the archaeal cell. The repeating element of the hexagonal lattice is composed of three identical protein chains, each rotated by 120 degrees relative to the others. Each chain has seven transmembrane alpha helices and contains one molecule of retinal buried deep within, the typical structure for retinylidene proteins.

It is the retinal molecule that changes its conformation when absorbing a photon, resulting in a conformational change of the surrounding protein and the proton pumping action.[3] It is covalently linked to Lys216 in the chromophore by Schiff base action. After photoisomerization of the retinal molecule, Asp85 becomes a proton acceptor of the donor proton from the retinal molecule. This releases a proton from a “holding site” into the extracellular side (EC) of the membrane. Reprotonation of the retinal molecule by Asp96 restores its original isomerized form. This results in a second proton being released to the EC side. Asp85 releases its proton into the “holding site,” where a new cycle may begin.

The bacteriorhodopsin molecule is purple and is most efficient at absorbing green light (wavelength 500-650 nm, with the absorption maximum at 568 nm).

Bacteriorhodopsin belongs to a family of bacterial proteins related to vertebrate rhodopsins, the pigments that sense light in the retina. Rhodopsins also contain retinal; however, the functions of rhodopsin and bacteriorhodopsin are different, and there is only slight homology in their amino acid sequences. Both rhodopsin and bacteriorhodopsin belong to the 7TM receptor family of proteins, but rhodopsin is a G protein-coupled receptor and bacteriorhodopsin is not. In the first use of electron crystallography to obtain an atomic-level protein structure, the structure of bacteriorhodopsin was resolved in 1990. It was then used as a template to build models of G protein-coupled receptors before crystallographic structures were also available for these proteins.

Many molecules have homology to bacteriorhodopsin, including the light-driven chloride pump halorhodopsin (for which the crystal structure is also known), and some directly light-activated channels like channelrhodopsin.

All other photosynthetic systems in bacteria, algae, and plants use chlorophylls or bacteriochlorophylls rather than bacteriorhodopsin. These also produce a proton gradient, but in a quite different and more indirect way involving an electron transfer chain consisting of several other proteins. Furthermore, chlorophylls are aided in capturing light energy by other pigments known as “antennas”; these are not present in bacteriorhodopsin-based systems. Last, chlorophyll-based photosynthesis is coupled to carbon fixation (the incorporation of carbon dioxide into larger organic molecules); this is not true for bacteriorhodopsin-based system. Thus, it is likely that photosynthesis independently evolved at least twice, once in bacteria and once in archaea.


  1. Voet, Judith G.; Voet, Donald (2004). Biochemistry. New York: J. Wiley & Sons. ISBN 0-471-19350-X.
  2. “Bacteriorhodopsin: Pumping Ions”.
  3. Hayashi S, Tajkhorshid E, Schulten K (September 2003). “Molecular dynamics simulation of bacteriorhodopsin’s photoisomerization using ab initio forces for the excited chromophore”. Biophysical Journal 85 (3): 1440–9. doi:10.1016/S0006-3495(03)74576-7. PMC 1303320. PMID 12944261.
  4. PDB Molecule of the Month pdb27_1
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