Tag Archives: research

NIH Trend: Grant funding success rate

The sequestration ordered on March 1, 2013 has led to 5% budget cut in the National Institute of Health (NIH) funding. NIH is a key player in funding scientific research. Based on their website, NIH states that there would be roughly 640 less projects granted in the fiscal year of 2013 compared to 2012.

nih success rate

Diagram 1: The continual decline of application success rate in NIH. The blue bar illustrated the number of applications. The green bar illustrates the number of awarded applications. The pink line illustrates the percentage of success rate.

From the NIH data book, we have extracted the success rate in diagram 1 (above). The success rate has dropped significantly from 30% in 2000 to 17% in 2013. That’s a whooping 13% drop in success rate when the number of applications continues to grow. If you look at the detailed number of awarded application (see below), the number of awards coming from NIH in 2013 is similar to the number of awards between 1998 and 1999. So, is NIH under-funded? Absolutely yes.

nih success rate data

Diagram 2: Decline in the number of awards to a level similar to 1999.

Let’s switch gear and look at the award of R01 success rate. R01 is the “original and historically oldest grant mechanism used by the NIH”. Diagram 3 below shows first-time applicant (blue) and established investigator (in green). It shows that both success rates have dropped significantly since the late 90s. Since mid-2000s, the success rate has plunged below 20%. The success rates for both first timer and established investigators are now at record low.R01 success rate

Diagram 3. Decline of R01 success rate is found in both first time and established investigators

Interestingly, the number of investigators getting the awards is on a steady increase since the late 90s (see diagram 4 below). Despite the number of awards granted in 2013 is similar to the late 90s, the number of investigators continue to increase. This is possibly due to the fact that more applicants are applying for a grant jointly. Furthermore, the decline in the number of awarded grant application has affected first time applicant the most.

R01 number of investigators

Diagram 4. Steady increase of the number awarded investigators since the late 90s. With the recent decline of awards from 2010, the first time applicants have taken the hardest hit.

Whether or not you are a first time applicant or an established investigator, time is tough. There is an steady increase amount of grant applications, while the number of awards plunges to the level from the late 90s. In the next issue, we will continue to look at the trend within graduate students and postdoctoral fellows.

Source: NIH RePORT

MRSA superbug: a global concern

There is an increasing amount of news coverage on the superbug, which is also known as the methicillin-resistant Staphylococcus aureus (MRSA). But how much do you really know? Here, I will talk about the reason why we should be concerned about the spread.MRSA trend

The history of this bacteria, Staph. aureus, can be traced back to the Egyptian mummies, which historians had recovered pathological changes that are consistent with staphalococcal osteomyelitis. Staph. aureus can be found in 20% to 45% of normal healthy adults. In the hospital-associated cases, serious infection is often caused by the bleach of protection. For example, the skin barrier protection is disrupted after going through an invasive surgery, which allows the colonization of Staph. aureus in tissues.

The concern of MRSA grows as the healthcare community now faces with strains of Staph. aureus that are equipped with methicillin and vancomycin resistance genes.

If you look at the timeline (from Nature Magazine), shortly after the introduction of penicillin in the 1940s, some strains of Staph. aureus were already found to have penicillinase/resistance to penicillin. And if you look at when methicillin is introduced to treat Staph. aureus infection, you can see that methicillin resistant strains can be found shortly after the introduction. Typically, vancomycin is used as a last resort due to its toxicity. But the resistance of vancomycin is also emerging.

Are we running out of options to treat Staph. aureus infection? Not now. But if we don’t take action soon to accelerate the antibiotics discovery, we will run out of options when vancomycin resistant strains dominate.

It’s just take take take with these GAS: Bacterial modulation of host cell metabolism

Infections generally follow a similar path with some consistent steps. The microbe gains entry to the host, replicates in the host and is shed, in order to spread to a new host. Commonly this has the unfortunate side effect of making the host a bit ill.

For bacteria, replication within a host relies upon, among other things (such as avoiding the murderous cells of the host immune system), the ability of the microbe to obtain essential nutrients from the environment it finds itself in. A study published in Cell now shows that the pathogenic bacterium, group A Streptococcus (GAS), uses a mechanism that directly modulates the metabolism of the host cells in order to stimulate its own replication and proliferation.

GAS causes a variety of human infections and in fact only infects humans. Causing the well-known “strep throat” the majority of illnesses involving this bacterium are relatively mild. This is because the bacterium is commonly only found on the skin or in the throat. If this changes and the bacterium finds its way into more internal tissues, the blood or lungs for example, severe disease such as necrotising fasciitis and streptococcal toxic shock syndrome can result. Worldwide there are 700 million cases of mild GAS infection with about 650,000 cases becoming severe invasive infections. These 650,000 cases are associated with a mortality rate of around 25%.

Upon entering the host it is important for the bacteria to quickly gather nutrients in order to proliferate and truly establish itself at the site of infection. GAS attaches to host cells and releases the toxins streptolysin O (SLO) and streptolysin S (SLS) into the host cell. These toxins stimulate endoplasmic reticulum (ER) stress within the host cell. ER stress causes an increased unfolded protein response, ER-associated protein degradation (ERAD) and eventually cell death through a variety of pathways. It is associated with a medley of diseases such as diabetes and Alzheimer’s disease. In this case the change we are interested in is the increase in production of the enzyme asparagine synthetase that catalyses the production of asparagine (ASN). The researchers found that the host cell secretes increased levels of ASN which are detected by the bacterium, causing a sweeping change in gene expression that affects nearly 17% of the bacterium’s genes. These changes in gene expression include the up-regulation of genes involved in proliferation. In the absence of ASN these genes were down-regulated and the production of SLS/SLO was increased.

Graphical representation of the described pathway Image credit: Cell
Graphical representation of the described pathway
Image credit: Cell

This mechanism was only active locally and temporarily upon initial attachment, implying that this is a mechanism used by GAS to establish infection early on. Interestingly the detection of the increased ASN uses the two component system TrxSR, which is heavily involved in regulation of the bacterium’s virulence and metabolic genes. The researchers claim that this demonstrates that this pathway is an “important attribute to GAS pathogenesis” and helps the bacterium to cause severe disease. Other bacterial pathogens have been reported to benefit from host cell metabolism modulation, such as Agrobacterium tumefaciens, which makes plant cells produce opines required by the bacterium. The scientists point out that there are other pathogenic bacteria that use SLS/SLO-like toxins such as S.aureus and L.monocytogenes (both known for their ability to ruin a good takeaway or cream cake) and that it would be interesting to see if they use similar pathways.