My friend Chris Taylor makes the best keychains. Many of them unfold to reveal internal structure, and they all come with fact sheets. I had trouble picking a few to show, because they are all amazing!
TOP TEN MOST IMPORTANT FEMALE SCIENTISTS THAT EVERYBODY NEEDS TO KNOW ABOUT
1. Ada Lovelace - A writer and mathematician and the daughter of famous writer Lord Byron, she is known historically as the world’s first computer programmer - even though computers weren’t invented for more than a hundred years after she died.
2. Marie Curie - A Polish chemist and physicist who, along with her husband, discovered both the phenomenon of radioactivity and two new elements (Radium and Polonium). She was the first woman to win a Nobel Prize, the only person ever to win twice in multiple sciences, and gave birth to two children who themselves went on to win a Nobel Prize, making the Curie family the recipients of five different Nobel Prizes.
3. Rosalind Franklin - While today it is two men, James Watson and Francis Crick, who get the credit for having discovered deoxyribonucleic acid (better known as DNA), it was actually a woman - Rosalind Franklin - who discovered the structure and properties of DNA. It was Franklin who theorized that DNA had a winding staircase structure, and she believed that phosphorus played an important role in the shape of DNA. Watson and Crick disagreed with her, though they later took the credit for her theories and discoveries.
4. Jane Goodall - Considered to be the foremost expert on chimpanzees on Earth, Jane Goodall is a British primatologist, ethologist, and anthropologist. She has done considerable work in the area of conservation and ethics and contributed greatly to our knowledge of primate behavior.
5. Gail Martin - After graduation, Dr. Gail Martin pioneered the field of stem cell research by discovering the method that we currently use to grow stem cells in a petri dish, which had previously been impossible. She also discovered that it was possible to harvest embryonic stem cells and, in fact, coined the term ‘embryonic stem cells’ itself.
6. Françoise Barré-Sinoussi - A French virologist who discovered that AIDS was caused by a virus, not some kind of “gay cancer”. Her contributions helped change public perception of HIV and AIDS as a “gay disease”, and likely saved many thousands of lives when she recommended ways to stop transmission between sexual partners (such as using condoms during sex).
7. Mary Claire-King - An American geneticist at the University of Washington, Mary Claire-King has studied the genetics of a wide range of topics, including HIV, lupus, deafness, and ovarian and breast cancer. Even in university, she was making waves: her thesis paper proved that the human genome and the chimpanzee genome were 99% identical. Later in her career, she helped pioneer a new type of treatment for breast cancer.
She also used her skill as a geneticist to help identify victims of human rights abuses by identifying children who had been illegally stolen from their families during wars, such as the Dirty War in Argentina.
8. Marie Tharp - A geologist in the 1970s and the only female in her entire department, Marie Tharp single-handedly rewrote everything that we currently know about geology today after a single discovery that she made one night. She hand-drew a map of the entire ocean floor and ended up discovering the Mid-Atlantic ridge, a series of underwater mountains and volcanoes which eventually caused a paradigm shift in the field of Earth sciences and led to the discovery of geological phenomena such as plate tectonics and continental shift. It took her years to gain credence for her theory, because her all-male department refused to accept her conclusion (until one of them, you know, actually took a look at her data). Both Marie Tharp and Annie Jump Cannon were mentioned by Neil deGrasse Tyson on different episodes of ‘Cosmos: A Spacetime Odyssey’.
9. Annie Jump Cannon - A deaf astronomer, Annie Jump Cannon and a group of other women were responsible for the development of a classification system based on color that we still use to this day to identify stars by.
10. Florence Nightingale - Most of us have probably heard this name before; and while she technically didn’t discover anything, she was single-handedly responsible for some reforms in the field of nursing that had enormous impacts on the way that nurses treat their patients, some of which are still practiced today (especially in undeveloped nations, where access to medical care is often sparse).
HIV virus particle, budding influenza virus and HIV in blood serum as illustrated by David S. Goodsell.
Goodsell is a professor at the Scripps Research Institute and is widely known for his scientific illustrations of life at a molecular scale. The illustrations are usually based on electron microscopy images and available protein structure data, which makes them more or less accurate. Each month a new illustrated protein structure can be found in Protein Data Bank molecule of the month section and you can read more on how his art is made here.
Many of us are familiar with the monarch butterfly (Danaus plexippus), but a research group is France has identified the genes for C-type lectins in this species most likely originated from parasitic wasps that are known to lay their eggs in the caterpillars of this species. These proteins are carbohydrate binding proteins with a large number of roles in cells.
Parasitic wasps are common in the insect world, with virtually all Lepidopteran species being targets for parasitism. It is believed that ~100 million years ago a wasp ancestor domesticated the bracovirus, and now these parasitic wasps employ it as a biological weapon against the caterpillars. The virus is produced in the wasp’s ovaries and acts as a vector for horizontal gene transfer (HGT). In the eukaryotic world, it is fairly rare for such an exchange of DNA between organisms.
The virus has long since lost its ability to generate a successful capsid, and as a result is reliant on the wasp’s ovaries for replication. The virus is injected into the host along with the wasp’s eggs where the domesticated virus promotes the growth of wasp progeny within the caterpillar by inhibiting its immune system. Each wasp lineage has its own set of virulence determinants encoded by the virus.
Integration of viral DNA may occur occasionally, if a caterpillar host manages to successfully defend itself against a parasitic attack or if the wasp lays its eggs in the wrong target. In both cases the caterpillar may go onto to develop into a moth or butterfly in possession of viral and wasp derived genes as seen in the monarch butterfly.
Figure showing the hypothesised process for HGT to occur between wasps and Lepidopteran species (Source)
Frustrated by the constant, inaccurate representations of viruses in textbooks and the media, Jerram was inspired to create his transparent and colorless Glass Microbiology series in 2004. To recreate each virus in glass as accurately as possible, he consulted with virologists from the University of Bristol. Jerram also collaborated with professional glassblowers such as Kim George, for help with the intricate and delicate pieces. Each handmade viral sculpture measures roughly one million times larger than the pathogen it represents.
“The discovery of more and more viruses of record-breaking size calls for a reclassification of life on Earth.”
The theory of evolution was first proposed based on visual observations of animals and plants. Then, in the latter half of the 19th century, the invention of the modern optical microscope helped scientists begin to systematically explore the vast world of previously invisible organisms, dubbed “microbes” by the late, great Louis Pasteur, and led to a rethinking of the classification of living things.
In the mid-1970s, based on the analysis of the ribosomal genes of these organisms, Carl Woese and others proposed a classification that divided living organisms into three domains: eukaryotes, bacteria, and archaea. (See “Discovering Archaea, 1977,” The Scientist, March 2014) Even though viruses were by that time visible using electron microscopes, they were left off the tree of life because they did not possess the ribosomal genes typically used in phylogenetic analyses. And viruses are still largely considered to be nonliving biomolecules—a characterization spurred, in part, by the work of 1946 Nobel laureate Wendell Meredith Stanley, who in 1935 succeeded in crystallizing the tobacco mosaic virus. Even after crystallization, the virus maintained its biological properties, such as its ability to infect cells, suggesting to Stanley that the virus could not be truly alive.
Recently, however, the discovery of numerous giant virus species—with dimensions and genome sizes that rival those of many microbes—has challenged these views. In 2003, my colleagues and I announced the discovery of Mimivirus, a parasite of amoebae that researchers had for years considered a bacterium. With a diameter of 0.4 micrometers (μm) and a 1.2-megabase-pair DNA genome, the virus defied the predominant notion that viruses could never exceed 0.2 μm. Since then, a number of other startlingly large viruses have been discovered, most recently two Pandoraviruses in July 2013, also inside amoebas. Those viruses harbor genomes of 1.9 million and 2.5 million bases, and for more than 15 years had been considered parasitic eukaryotes that infected amoebas.
Now, with the advent of whole-genome sequencing, researchers are beginning to realize that most organisms are in fact chimeras containing genes from many different sources—eukaryotic, prokaryotic, and viral alike—leading us to rethink evolution, especially the extent of gene flow between the visible and microscopic worlds. Genomic analysis has, for example, suggested that eukaryotes are the result of ancient interactions between bacteria and archaea. In this context, viruses are becoming more widely recognized as shuttles of genetic material, with metagenomic studies suggesting that the billions of viruses on Earth harbor more genetic information than the rest of the living world combined. These studies point to viruses being at least as critical in the evolution of life as all the other organisms on Earth.
The first of 50 patients to complete a trial for a new HIV treatment in the UK is showing no signs of the virus in his blood.
The initial signs are very promising, but it’s too soon to say it’s a cure just yet: the HIV may return, doctors warn, and the presence of anti-HIV drugs in the man’s body mean it’s difficult to tell whether traces of the virus are actually gone for good.
That said, the team behind the trial – run by five British universities and the UK’s National Health Service – says we could be on the brink of defeating HIV (human immunodeficiency virus) for real.
“This is one of the first serious attempts at a full cure for HIV,” Mark Samuels, Managing Director of the National Institute for Health Research Office for Clinical Research Infrastructure, told Jonathan Leake at The Sunday Times.
“We are exploring the real possibility of curing HIV. This is a huge challenge and it’s still early days but the progress has been remarkable.”
Bacteriophages: Antibiotic Alternative or Just a Phase?
It is now clear that we are rapidly approaching a post-antibiotic
era, and the need for an alternative is more vital than ever. The CDC estimates
that approximately 2 million people are infected with antibiotic resistant
bacteria each year, and of that 23 000 of them die as a result of the infection
. Our antibiotic pipeline is drying
up and the development of new antibiotics is both slow and expensive, making
antibiotics unappealing investments for pharmaceutical companies. Although
alternatives to antibiotics are far from the market, the field is slowly expanding.
Amongst the alternatives, bacteriophages (phages) are a potential candidate for
both diagnostic and therapeutic medicine.
Quite simply, phages are viruses that infect bacteria. These
are the most abundant biological entity on the planet and are thought to
outnumber bacteria 10:1. Their sheer abundance has led to a vast diversity that
has yet to be exploited by modern medicine. This is in part due to a number of
problems with phages that haven’t made them ideal candidates for therapy. This
article seeks to look at some of the problems with phages, and what steps are
being taken to improve them for application in humans.
Rapid clearance from the host:
Delivery systems for phages have not been thoroughly assessed for systemic phage application. In other words we are still lacking a way of delivering a bacteriophage drug intravenously to ensure that phages have the maximal effect on the patient. Annoyingly, our immune systems are great at rapidly inactivating and removing them from our bodies , with animal studies showing that phage can be completely cleared within 24 hours . Early work carried out in germ-free mice in the 70s showed that phages are passively collected in the mononuclear phagocyte system (MPS), where they remain viable until inactivated by immune cells .
There have been two solutions developed so far to amend this problem . The first was developed in the late 90s by the National Institute of Health in the US, which involved the serial passage of phage through a living organism. It was hypothesised that some phage would have mutations in their coat proteins that would give them increased protection from the natural filtration systems in the body over wild type phage  and by selecting for these phage, you could gradually produce a population of long-circulating phage. When applied, these phage would have longer circulation times, and therefore a greater chance of colliding with their target bacteria. Animal studies have shown far better recovery of animals given long-circulating strains of virus over wild type, when presenting symptoms of otherwise fatal bacteraemia .
Figure 1. Diagram showing a few of the possible receptors for Salmonella sp. phage 
Additionally, to prevent degradation or inactivation of phages, polymers can be added to the coatings of phages . The polymer polyethylene glycol (PEG) has been shown to increase systematic circulation and decrease T-helper cell activation in response to phage. It is likely that a combination of these two methods may improve delivery strategies in the future of phage therapeutics.
Altering host range and preventing resistance:
Unlike antibiotics, phages have incredibly refined, narrow host-ranges. This property is in reality a double edged sword: in many cases, phages are only able to target a few strains of a single species, whereas antibiotics relentlessly target multiple branches of the bacterial phylogenetic tree. Antibiotic treatment can lead to disruption of the host’s own microbiota which can permit the colonisation of nastier and less cooperative microorganisms.
In contrast, phages can target their host whilst leaving the surrounding organisms in relative peace. When a patient presents symptoms of infection, the particular species or strain causing the infection would be unknown. Identifying the culprit before selecting the right phage would take time a patient may not have.
Receptors on the bacterial cell surface are what determine which phage are able to bind to the cell. A wide variety of receptors are used by phage, but many still remain a mystery. To curtail these issues and ensure that as many receptors can be targeted for a particular bacterium, phage cocktails are used . These are mixtures containing a number of different phage strains. In theory, the cocktail should be designed so that the phages together should be able to target all the known clinically relevant strains of a particular species of bacteria.
Creating phage cocktails from natural sources can be laborious , however viral DNA provides a platform for genetically engineering phages with desired properties. Improving phage cocktails with modified phages expressing structures that could target a wide variety of receptors on a bacterial cell could ensure that a cocktail could target the maximum number of strains, whilst reducing the selection pressure on a sole receptor. Resistance to the phage cocktail would then also be avoided.
Much of this work looks at genetically engineering phage tail fibres [7, 8]. These ‘spider-leg’ like components regulate the initial binding step between a phage and a target cell. It has been shown by Mahichi et al, 2009 and Ando et al, 2015 that switching tail fibres between phages with different host ranges can confer host-range specificity from one phage to another. Hopefully, modular engineering of phages will push phage technology forwards, offering new strategies for developing phages for therapeutic purposes.
Figure 2. Diagram showing how the modular shuffling of tail fibres between viral strains can confer host range of parental strain .
Preventing the release of cellular toxins
A major health risk of phage, is that like β-lactam antibiotics, they interfere with the bacterial cell wall integrity and ultimately lead to cell lysis. Lysing cells prevents further replication, but also releases all the cell’s content. This may include but not be limited to superantigens and lipopolysaccharides (LPS) . These toxins will trigger the inflammatory response, and in extreme cases cause organ failure and death.
Phages have a simple dual-lysis system consisting of a holin and endolysin. The holin is a pore-forming membrane protein that creates an exit from the cytoplasm for the endolysin. The endolysin is then able to attack the peptidoglycan of the bacterial cell wall, resulting in its rupture. To generate phage incapable of lysing a cell, the dual lysis system simply needs to be inactivated.
To restore killing power to the phage in the absense of the dual lysis system, a bacterial toxin needs to be incorporated into the phage genome. Hagens et al, 2004 has shown that by engineering the filamentous phage M13 to encode a non-native restriction enzyme, antimicrobial activity can be restored through the generation of double stranded breaks in chromosomal DNA. Upon infecting Psuedomonas aeruginosa with this phage, there was a 99% drop in viable cell counts over the time course . Other research has looked into other uses for the non-lytic killing of bacteria, including proteins that interfere with regulatory systems and other bacterial toxins.
Phage therapy has shown promise in recent years as being a good candidate for either working in synergy with or replacing antibiotics. The appalling lack of human based clinical trials haven’t helped to expose their potential for human use. Although this is the case, a significant amount of work has been done on improving phage therapy in preparation for further studies with human application. The past 15 years have seen an improved outcome for this technology as obstacles with phages are gradually manoeuvred by intelligent reengineering. With hindsight we have now acquired through our experiences with antibiotics, hopefully we will not make the same mistakes with phages as we have done with antibiotics.
1. CDC (2013) Antibiotic resistance threats. US Dep Heal Hum Serv 22–50
2. Lu TK, Koeris MS (2011) The next generation of bacteriophage therapy. Curr Opin Microbiol 14:524–531
3. Carlton RM (1999) Phage therapy: past history and future prospects. Arch Immunol Ther Exp (Warsz) 47:267–274
4. Merril CR, Biswas B, Carlton R, Jensen NC, Creed GJ, Zullo S, Adhya S (1996) Long-circulating bacteriophage as antibacterial agents. Proc Natl Acad Sci U S A 93:3188–3192
5. Chaturongakul S, Ounjai P (2014) Phage host interplay: examples from tailed phages and Gram-negative bacterial pathogens. Front Microbiol 5:1–8
6. Moradpour Z, Ghasemian A (2011) Modified phages: Novel antimicrobial agents to combat infectious diseases. Biotechnol Adv 29:732–738
7. Ando H, Lemire S, Pires DP, Lu TK (2015) Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing. Cell Syst 1:187–196
8. Mahichi F, Synnott AJ, Yamamichi K, Osada T, Tanji Y (2009) Site-specific recombination of T2 phage using IP008 long tail fiber genes provides a targeted method for expanding host range while retaining lytic activity. FEMS Microbiol Lett 295:211–217
9. Hagens S, Habel A, Ahsen U Von, Gabain A Von (2004) Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage. Antimicrob Agents Chemother 46:3817–3822
Herpes infected humans before they were human 1.6 million years ago
Researchers at the University of California, San Diego School of Medicine have identified the evolutionary origins of human herpes simplex virus (HSV) -1 and -2, reporting that the former infected hominids before their evolutionary split from chimpanzees 6 million years ago while the latter jumped from ancient chimpanzees to ancestors of modern humans – Homo erectus – approximately 1.6 million years ago.
The findings are published in the June 10 online issue of Molecular Biology and Evolution.
“The results help us to better understand how these viruses evolved and found their way into humans,” said Joel O. Wertheim, PhD, assistant research scientist at the UC San Diego AntiViral Research Center and lead author of the study. “Animal disease reservoirs are extremely important for global public health. Understanding where our viruses come from will help guide us in preventing future viruses from making the jump into humans.”
Approximately two-thirds of the human population is infected with at least one herpes simplex virus. The viruses are most commonly presented as cold sores on the mouth or lips or blisters on the genitals.
“Humans are the only primates we know of that have two herpes simplex viruses,” said Wertheim. “We wanted to determine why.”
The researchers compared the HSV-1 and HSV-2 gene sequences to the family tree of simplex viruses from eight monkey and ape host species. Using advanced models of molecular evolution, the scientists were able to more accurately estimate ancient viral divergence times. This approach allowed them to determine when HSV-1 and HSV-2 were introduced into humans with far more precision than standard models that do not account for natural selection over the course of viral evolution.
The genetics of human and primate herpes viruses were examined to assess their similarity. It became clear that HSV-1 has been present in humans far longer than HSV-2, prompting the researchers to further investigate the origins of HSV-2 in humans.
The viral family tree showed that HSV-2 was far more genetically similar to the herpes virus found in chimpanzees. This level of divergence indicated that humans must have acquired HSV-2 from an ancestor of modern chimpanzees about 1.6 million years ago, prior to the rise of modern humans roughly 200,000 years ago.
“Comparing virus gene sequences gives us insight into viral pathogens that have been infecting us since before we were humans,” said Wertheim.
Bats are quite a fascinating animals from an emerging infectious disease point of view. There is just something about their biology that allows them to harbour large numbers of viruses, apparently, without a lot of of side effects. Exactly what that something is is not clear as it’s quite difficult to study large colonies of bats but it may be linked to unique features of their behaviour and, at the molecular level, components of their immune system. In one study scientists were able to isolate sequences of 58 different viruses from one bat, and sampling of bats has shown that they can be carriers or have themselves encountered Ebola, Nipah, Hendra, Rift Valley Fever and other viruses.