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Dr. Marie Gabrielle Laguna

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Medical doctor-internist

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Combination Drug Holds Promise in Breast Cancer Treatment

Jan 24, 2016

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In a new research by the Perelman School of Medicine of the University of Pennsylvania, the�combination of the new breast cancer drug palbociclib with paclitaxel (Taxol) was able to reduce the�size of tumors in almost half of the patients who are stricken with estrogen-receptor (ER) positive breast�cancer.

Further study also showed why breast cancer develops resistance to palbociclib, which
commonly occurs in patients who are taking the drug for treatment.

Angela DeMichele, MD, MSCE, who is the senior author of the study, and the Alan and Jill Miller Associate
Professor in Breast Cancer Excellence in Penn's Abramson Cancer Center, says that the results of the study
indicate that both palbociclib and paclitaxel can be safely used together if used on an alternating dosing
schedule. The high response rate we saw suggests this combination may hold benefits for patients over
paclitaxel alone. Based on these results, a larger clinical trial to determine the benefits is warranted,� says
DeMichele.

Palbociclib acts by inhibiting the activity of CDK4 and CDK6, which are enzymes that help in cell
proliferation and are upregulated in most cancers. The researchers hypothesized that this drug might be
good in combination with other drugs, such as paclitaxel, that try to kill cancer cells at a certain point in
the cell cycle. Palbociclib is able to halt the cycle before the cell completely divides, which means that
drug can make the cancer cells more vulnerable to a consequent dose of paclitaxel.

Breast Cancer Treatment

DeMichele and colleagues treated 27 patients with alternating doses of 75 mg per day palbociclib, which
was given daily for several days, and paclitaxel, given once a week. Around 44% of the patients had a
partial or complete response rate, and four additional patients had a stable disease for 6 months or longer.
The results suggested that the alternate dosing of the two drugs is safe to use for larger-scale trials.
Unfortunately, most patients experienced side effects such as neutropenia, which is a condition where
the white-cell-blood count is low. This is actually a common side effect of palbociclib and other drugs used
for cancer, but DeMichele says it is not threatening in general. In order to deal with this, the dose for some
of the patients was lowered.

In another study, DeMichele teamed up with palbociclib's maker, Pfizer. The aim this time was to
determine why breast cancer is able to develop resistance to the drug. Examining samples taken from a
patient who was undergoing treatment with palbociclib, the researchers found that while the tumors
were becoming resistant to the drug, the expression of several cell-cycle promoting genes such, as PLK1,
TOP2A, CDK1 and BUB1, were more than doubled. Cell cultures of tumor cells that have palbociclib
resistance also showed the same results.

It appears that while the drug blocks two important cell-cycle drivers, CDK4 and CDK6, other cell cycle
genes can compensate with increased expression levels to enable tumor cells to start dividing again,� says
DeMichele. This implies that another drug that blocks these other cell cycle genes would be needed to be
able to prevent the resistance against palbociclib that is happening.

Childhood asthma genetic variant can be neutralized, say scientists

Jan 23, 2016

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A new study from the Ludwig-Maximilians-Universitaet (LMU) has discovered that the effect of a�genetic variant that increases the likelihood of having childhood asthma can be neutralized.

The study�was also able to show that young infants are benefiting to the positive effects of exposure to farm dust.

Asthma scientists from LMU in Munich have shown that specific environmental experiences and
influences can actually neutralize the effect of a prevalent genetic variant that poses a risk for the
development of childhood asthma. The same study was able to show that those that have this genetic
variant are also very responsive to environmental factors that are able to provide long term protection
against asthma. Children who had the genetic variant and were exposed to airborne microorganisms in
animal sheds before their first birthday were found to be more resistant to infections of the lower
respiratory tract as compared to those who had the genetic variant and hadn't been exposed to farm
animals in the early stages of their lives.

The study was conducted by Markus Ege, Professor of Pulmonary Epidemiology at Dr. Von Hauner's
Children's Hospital, together with Professor Erika von Mutius, Director of the Outpatient Clinic for Asthma
and Allergy, and first author Dr. Georg Loss, who is a member of von Mutius' team. It was published in the
American Journal of Respiratory and Critical Care Medicine. We can conclude from this observation that
these children are also less likely to develop asthma later on than carriers who did not benefit from the
�farm effect',� says Professor Ege.

The data was acquired from the long-term epidemiological study Pasture�. They were in the form of
weekly diaries from around 1000 mothers who were recruited for the project and were residents in
predominantly rural regions. The mothers recorded details of the early development of their children
starting from birth and until the children reached 6 years of age. The diaries contained many information
including occurrences of respiratory illnesses and noted how much time the children spent in the farms.
When the researchers focused on the children that had a known genetic variant for asthma, which is
located on the q21 region of chromosome 17, they found out that carriers of the variant that were
exposed as infants for at least 2 hours a week to the air in animal sheds had an 80% drop in the occurrence
of wheezing, as compared to carriers of the variant in non-farm settings.

Childhood Asthma

Children who spend a lot of time with farm animals usually inhale small particles of hay and grass. Along
with these particles are many microorganisms such as bacteria, fungal cells and spores, as well as pollen
grains, which are carried into the airways. When these microorganisms reach the respiratory epithelium
that line the airways, they modulate the inflammatory response in the body. The ultimate goal of the
researchers is to discover what exactly causes this so-called farm effect�, as this knowledge would truly
be helpful in developing new strategies that would be able to help prevent asthma. This is especially true
since having the genetic variant is not at all rare, which is estimated to be about 75% of the population.

Untangling Diseased Proteins

Dec 11, 2015

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Scientists have discovered that essential proteins aggregate to become defective proteins.

A lot of severe diseases involve the build-up or aggregation of misshaped proteins. Recently, a team of scientists from the University of Cambridge has discovered a new property of essential proteins which might be directly involved with protein aggregation when it becomes defective.

Most neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, have one common trait: they involve the build-up of �misfolded' proteins, which then cause damage to the brain.

This is also seen in other forms of diseases, such as motor neuron disease (or amyotrophic lateral sclerosis, ALS), and frontotemporal dementia. In such diseases, there is the build-up of misfolded FUS protein as well as other RNA-binding proteins. However, the mechanism of aggregation of this type of protein has several differences with conventional protein aggregates seen in Alzheimer's or Parkinson's. Because of this, until now, it is unclear how FUS proteins aggregate and the significance of this aggregation is still unknown.

FUS, as mentioned earlier, is an RNA-binding protein, and is involved in RNA transcription regulation as well as the translation of RNA into proteins. In line with these functions, they have domains to bind RNA, and also domains where the protein still appears to be unfolded or unstructured.

FUS Proteins

According to the journal published in Neuron by scientists from the University of Cambridge, FUS proteins are able to transition between a completely soluble �monomer' form, and a condensed jelly-like form known as a hydrogel. While these transitions are happening, the protein assemblies capture and release RNA and other proteins. This allows for efficient transcription and translation without the use of a limiting membrane.

Using C. elegans as an ALS and frontotemporal dementia model, the study revealed that the transition from monomer to hydrogel could sometimes become irreversible. In the case of FUS and other RNA binding proteins, the �healthy' proteins rarely spontaneously over-condense. However, if FUS becomes mutated, the condensation process becomes excessive and forms thick gels that are unable to return to the monomer state. Because of the formation of these thick gels, some important proteins and other structures (such as ribosomes) become trapped and are also unable to serve their function. It also disrupts the synthesis of new proteins in nerve axons.

The research was able to show that the formation of these irreversible jelly-like structures can be prevented by targeting with small molecules, thereby rescuing the worm from impaired motility and extending its lifespan.
So basically, the research shows that some proteins are able to morph from a soluble state to viscous hydrogels that allows cells to efficiently perform cellular processes, and then disassemble the machinery back to its soluble state when not needed. This seems to be more effective as compared to doing the same thing inside intracellular membrane-bound vesicles. Unfortunately though, this process can become excessive because of mutations, leading to disease.

From the team, Professor St George Hyslop says that they have shown that some proteins are able to transition between states, but this property is also a double-edged sword, in that when a mutation is present, their normal function is easily disrupted, causing disease.

The same principles are likely to be at play in other more common forms of these diseases due to the mutation in other related binding proteins. Understanding what is in these assemblies should provide further targets for disease treatments�.

Prof Hyslop also says that this is also a good example of how bringing together people from the biological and physical sciences has been able to reveal the underlying causes of a disease, and also shows the importance of considering the mechanisms of disease not only as plainly biological, but also physical.

If you want to know more about proteins and their functions, feel free to read our other articles on this site.

Written by: Yevgeny Aster Dulla, MSc.

Divorce Rate Inversely Proportional With Disabled Children’s Family Size

Dec 10, 2015

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Based on a new study from the University of Wisconsin-Madison's Waisman Center, if a couple raises a child with developmental disabilities, increasing the number of children does not increase the risk of divorce.

This study was published in the American Journal on Intellectual and Developmental Disabilities. The study also compared couples who have at least one child with developmental disorders to couples who have normally developing children.

Disabilities and Divorce

According to the study, for couples who don't have children with disabilities, the risk for divorced increased as the number of children increased. On the other hand, for couples that do have a child with developmental disabilities, an increase in the number of children did not affect the risk of divorce.

For sure, raising a child with developmental disabilities is not an easy feat. The challenges and rewards that are involved vary, and are quite different for each family. However, research has also shown that parents with a child that has developmental disability tend to experience more marital stress as compared to couples raising normally developing children.

Because of this concept, people have been thinking that couples who have a child with developmental disabilities are more likely to get a divorce. The aim of the study was to actually test this assumption according to Eun Ha Namkung, a graduate student who is the first author of the paper.

Based on the results of the study, it was found that couples with typically-developing children experience less marital stress, because these other children are able to care for and support their siblings that have developmental disabilities.

Around 22 percent of couples with a child that has developmental disability had a divorce during the length of the study. In the comparison group, 20 percent experienced divorce, and it is clear that there is no significant difference between the two.

Namkung's team used the Wisconsin Longitudinal Study (WLS) as the basis of their research. The WLS is a project that has been following more than 10,000 males and females, as well as some of their siblings, who graduated from high schools in Wisconsin since 1957. This project was able to provide a very rich and random sample source for Namkung's study.

Within the WLS, the researchers were able to take note of the lives of 190 couples whose children had a broad range of developmental disabilities, which include autism spectrum disorders, Down syndrome, cerebral palsy, among others.

Even though the use of the WLS was very advantageous, Namkung also pointed out a few limitations of its use. The population described in the study was mostly of Caucasian descent, which meant there was little or no ethnic diversity involved in the study. Most of the participants were also born between 1930�and 1935, and it is possible that the analysis of data from younger generations would show a different set�of results regarding divorce rates.

The shortcomings involved in the use of WLS are what Namkung and colleagues aim to tackle in the future.
They also plan to focus on other types of disabilities such as mental illness in order to understand the
specific effect of having a child with a specific disorder on divorce rate.

Written by: Yevgeny Dulla, MSc

Women Who Had Bariatric Surgery Can Give Birth to Diabetic and Obese Children

Dec 9, 2015

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The Benefits of Bariatric Surgery

In the old days, if you were fat, people would think that you were rich and healthy. Fat was associated with a higher socioeconomic status– until fat people began to die from disease earlier than other people. These deadly diseases that continue to haunt obese people were diabetes, heart attack and stroke. This is why recently there is a move by government agencies to encourage more people to lose weight.

If you have resistant fat, it would be very hard for you to lose weight. Increased abdominal circumference has been found by studies to give rise to more complications and more disease. This is due to the fact that abdominal fat is an unhealthy type of fat that can give rise to elevations in blood sugar, high blood pressure and atherosclerosis– all bringers of stroke, heart disease, blood vessel disease and death. In obese people who cannot lose abdominal fat with diet and exercise, bariatric surgery may be beneficial.

Bariatric surgery is a highly recommended surgical procedure to lose abdominal fat fast. It is said that within two to three years after the performance of bariatric surgery, there is an expected weight loss of about 10 to 35 percent of the total body weight. This depends on the procedure that you will choose. People who will undergo bariatric surgery should talk to their doctors about their expectations and about their weight loss. The benefits include remissions in co-morbidities such as sleep apnea, high blood pressure, diabetes and other diseases. These diseases may also permanently disappear with bariatric surgery. People who have undergone bariatric surgery may actually decrease their need for medicines and may not even need their medicines at all.

In women, the benefits of bariatric surgery are many. This procedure is said to boost fertility in women and even reduce the risk of pregnancy complications that commonly may occur in women. These pregnancy complications may include preeclampsia and gestational diabetes.

Obese And Diabetic Offspring

However, in the light of all these benefits, a recent study done by researchers from the�University of Mississippi Medical Center have found out that bariatric surgery may have negative consequences on children who were born to mothers who had undergone the procedure. These new findings were presented at the�Cardiovascular, Renal and Metabolic Diseases: Physiology and Gender.

The researchers of this study have previously observed that rats which were born to mothers that have undergone�vertical sleeve gastrectomy (VSG), a type of bariatric surgery in which 80% of the stomach is removed, were smaller than normal and that they were more prone to develop diabetes and obesity. The team has observed hat these female rats who underwent bariatric surgery had smaller pups. Their placentas also had greater activation of genes which are involved in inflammation and the lack of oxygen. These data only showed that these hormonal and chemical changes induced by bariatric surgery may lead to reduced fetal growth. Thus the researchers concluded that the benefits of bariatric surgery on women may have negative consequences on their offspring.

If you want to read more about diabetes and obesity, feel free to browse our other articles on this site.

Fiber- The Missing Link Between Nutrition And Good Health

Dec 8, 2015

2901

Fiber should be in our diet.

We sure have heard of several diet fads claiming to make you lose weight in as little as a few days after trying them. It does faze us for awhile but its time for us to know the facts.

Fiber is known for its tummy friendly benefits but little is known about its other potentials to improve health well-being. As little as 10 grams of fiber each days increases your life expectancy by 10% and some studies claim that fiber lowers all cause mortality by 15%.

Individuals who incorporated healthy fiber in their diet have an increased life expectancy in the next 9 years by 25%. Those fond of Mediterranean diet have an added benefit of greater resistance to inflammatory conditions brought about by the saturated fatty acids from digested organic fiber.

Fermentation of food by intestinal bacteria brings about the production of short chain fatty acids that decreases the individuals risk for diabetes mellitus and cardiovascular disorders. Recent studies have also shown that these fatty acids contribute to strengthening the T cells thereby increasing their capacity to combat infection and hastens the oxidative function of the liver and the adipose tissue.

Elevated blood sugar levels in the circulation acts as a nidus to infections caused by yeast and can also cause sinus infections. Organic fiber and chia seeds can bring blood sugar levels to near normal to normal values by reducing hunger pangs most commonly observed in people with less fiber intake, lowers cholesterol levels thereby reducing cholesterol plaque formation and stroke risk.

Fiber in Mushrooms?

Recent studies focused on the benefits of mushrooms as a dietary fiber. Five types of mushrooms were evaluated for their fiber content in decreasing order namely Chantarelle, Maitake, Button, Oyster and Shitake. So, its time to look at mushrooms in another light other than being sat on by a leprechaun ei?

People have become more aware of the presence of carcinogens in our diet. It is best to do away from pesticide laden grains. These grains are thought to enhance our metabolism but the fact is since a substance called glyphosate is being used to eliminate the weeds, it is being considered as a likely carcinogen.

The fiber present in fruits, vegetables, grains and nuts are considered as organic fiber. Psyllium husk and sunflower sprouts are loaded up with all the essential amounts of fiber great to support regularization of abnormal bowel movement.

Loading up on these fiber sources makes one both fit and healthy at the same time. As the popular ad says, Have you had your fruit today?� Go on and munch or even gobble up fibre rich food to a better life.

Written by: Dr. Christine Ena Carado

THE OSSEUS OF THE MATTER: Minerals and Beyond

Dec 7, 2015

2759

Bones in Our Body

There are 206 bones in our body and each of these bones from the largest to the teeny weeny ones have their specific function, because if they don't then God must not have placed them there right?

In this fast-paced life, fast-food seems everyone's best friend. Imagine not having to wake up early to prepare breakfast, the kids lunch and after a long days work- dinner. Having a wide array of choices is just what we need to have a hearty meal but experts says otherwise. Frequent visits to the fast-food joints not only ups your sugar content but devoid of nutrients necessary for our childrens growing body. Needless to say, the food is an answer to their cravings but yet poses a risk of serious bone problems in the near future.

Many studies have already postulated the harmful effects of fast-food diet and that includes high cholesterol, increased risk of diabetes in both children and adults and coupled with the gradually increasing number of childhood obesity. A single meal from the fast food counter contains enough calories to complete your average daily requirement for caloric intake.

Bone Mineral Density �and Food

It is in this light that the University of Southampton Lifecourse Epidemiology Unit did a study on the bone mineral density and content in several children. These 2 parameters were measured at birth and repeated at 6 years of age and correlated with the number of fast-food joints in the vicinity and the results were not significant statistically compared to those children with neighborhood stores selling organic products who have higher bone mineral density.

The International Osteoporosis Foundation suggested that mothers should advocate and choose the appropriate food for their childrens consumption. For growing children, having an increased bone mineral density is essential to prevent bone breakage since at this age children tend to explore and be physically active.

Foods that can increase bone minerals include breakfast cereals, soy milk, yogurt, orange juice, cheese, sardines, broccoli. Vitamin D intake is also essential to absorb all the calcium taken in by diet. Lesser Vitamin D in the circulation can hasten bone loss and lead to multiple fractures during old age.

Though it will take several more studies to verify the link between easy access to fast food and decreased bone mineral density in children, it is still noteworthy that the environment or eating habits that the child is exposed to is essential to their overall health.

Written by: Dr. Christine Ena Carado

Drink Up For Good Health: Surprising Benefits Of Red Wine

Dec 6, 2015

3030

In the past decade, alcohol consumption has become a growing habit that has influenced approximately half of adolescent and elderly population.

Our generation has been long aware that alcohol does not bring the body any good. Researchers have taken into consideration the health benefits that the right alcoholic drink when taken in moderation can give one's body innumerable benefits.

Recent studies focusing on the benefits of regulated consumption of alcohol containing beverages such as red and white wine were done among select diabetic individuals randomized control trials have yet to prove it. Diabetes has been shown to increase the risk of developing atherosclerosis by 5 fold than non-diabetic patients hence, to date the subject of many studies.

The Red Wine Study

Red and white wine given at moderate amounts (150ml) to diabetic individuals who agreed to participate in the study provided that they will not be operating or driving any machinery after intake were monitored for the improvement on their cholesterol and triglyceride levels. This study was conducted for a period of 2 years taking into consideration any additional medications and unexpected side effects the patient may experience while being enrolled in the study.

Participants are diagnosed diabetics who have well controlled blood sugar levels were divided into 2 groups on the results of ADH enzyme testing and labelled accordingly depending on the rate alcohol is being excreted from their system.

Among the 2 groups, those who excrete alcohol from their system slower were able to derive more benefit from intake of red wine having a more improved blood sugar control as compared to those participants who excrete alcohol faster from their body. Excellent sleep quality was reported from both groups.

Resveratrol found in grape peelings and subsequently present in red wine is said to be responsible for its effects in improving the ratio of cholesterol and lipoprotein levels and even when separately analyzed thereby backing up previous literatures showing that the health perks derived from red wine comes from its non-alcoholic components. Ethanol plays an important role in the metabolism of glucose by virtue of its interaction with the genetic makeup of the participants causing a beneficial effect in glucose levels.

Another study classified patients into three subgroups that will consume 5-ounce serving of either mineral water, white and red wine depending on the beverage assigned to them. Participants consume high amounts of fish, moderate intake of dairy products and little or none at all of meat and non-fish products through a 3 month period. Adherence and compliance to the program regimen were checked routinely together with their chemistry panels and imaging studies were also utilized to monitor any progression on the size of the cholesterol plaques.

If you want to read more about the benefits of red wine, feel free to read our other articles on this site.

Written by: Dr. Christine Ena Carado

Vitamin D Lowers Heart Disease Risk

Dec 5, 2015

3650

Vitamin D can boost your exercise performance and lower your heart disease risk.

According to a study presented at the annual conference of the Society for Endocrinology held at Edinburgh, taking vitamin D can actually improve your exercise performance and lower your risk of having a heart disease.

Vitamin D is known to be both a vitamin and a hormone, and has its main functions in the maintenance of the levels of calcium and phosphate in the blood, and is important in the formation of bones and teeth. Apart from this, vitamin D has also other important functions such as immunomodulation and the like. Natural sources of vitamin D include oily fish and eggs, but acquiring vitamin D from diet alone is not enough to reach the daily recommended intake. Humans usually generate most of their vitamin D by exposure of the skin to ultraviolet rays in sunlight. Ultraviolet B rays convert 7-dehydrocholesterol found in the skin to vitamin D.

The Benefits of Vitamin D

Previous researches suggest that vitamin D has the ability to block the action of the enzyme 11-HSD1, which is the enzyme involved in the production of the stress hormone cortisol. High levels of cortisol have various effects, such as constricting arteries and narrowing blood vessels (causing high blood pressure), as well as stimulating the kidneys to retain water. As mentioned, vitamin D has the indirect ability to lower levels of cortisol, which means that it could theoretically improve exercise performance and lower risk factors for cardiovascular diseases.

The study was conducted by researchers from Queen Margaret University in Edinburgh. Thirteen healthy adults were matched by age and weight and were given 50 mg of vitamin D per day or a placebo for a period of two weeks.
Adults who were taking vitamin D were observed to have lower blood pressure compared to those taking placebo, and were also seen to have lower levels of cortisol in their urine. A fitness test was also conducted against the subjects, and the group that was taking vitamin D was able to cycle at an average of 6.5 km in 20 minutes, compared to the baseline of 5 km at the start of the study. Even though the group taking vitamin D cycled 30% further in the same time, they also showed lower signs of physical exertion as compared to the placebo group.

In England, around 10 million people are thought to have low vitamin D levels in their body. One in ten adults have low vitamin D levels, whereas there are two out of five people during winter. Skin color is actually also a factor in vitamin D production in the body. People with darker skin are known to be less efficient in using sunlight to produce vitamin D, so up to three out of four adults with dark skin are vitamin D deficient in winter.

Dr. Raquela Revuelta Iniesta, co-author, says that the pilot study shows that taking vitamin D as a supplement is able to improve fitness level and lower cardiovascular risk factors such as blood pressure. They plan to perform a larger clinical trial for a more extended period of time and in both healthy individuals as well as specific groups of people such as athletes.

Vitamin D deficiency is a silent syndrome linked to insulin resistance, diabetes, rheumatoid arthritis, and a higher risk for certain cancers,� says Dr. Emad Al-Dujaili, lead author. He believes that their study adds to the treasury of information that shows the importance of taking on a widespread problem such as vitamin D deficiency.

To know more about the wonders of Vitamin D, feel free to browse our other articles on this site.

Written by: Yevgeny Aster Dulla, MSc

Tuberculosis enzyme structure discovered

Dec 3, 2015

2589

Tuberculosis enzymes being studied by scientists can pave the way for discovering anti-tuberculosis drugs.

Scientists, mostly from the US Department of Energy's Argonne National Laboratory, were able to reveal the structures of a number of important tuberculosis enzymes, which could possibly pave a way to finding new drugs for the disease.

Tuberculosis is a relatively common disease, affecting about one third of the world's population, and is caused by the bacteria Mycobacterium tuberculosis. It is a very stubborn disease and treating it can actually take up to nine months. Because this bacteria has the ability to hide inside the body's cells, the immune system is not able to detect it, and it only waits for a good opportunity to multiply. Aside from that, it also is fast in acquiring resistance to antibiotics.

In order to find drugs that work against this microorganism, scientists need to browse through the myriad of proteins that bacteria possess and find one that is very important to this specific bacteria that it will not survive without it, and make a drug that particularly targets this protein.

One target that is being considered is IMPDH (inosine-5-monophosphate dehydrogenase), which is involved in a process inside bacterial cells that produces the guanine nucleotide, which is essential for both the production of DNA and RNA. It is a very important compound such that practically all living organisms have their own versions of it.

The IMDPH Enzyme

Andrez Joachimiak, an Argonne Distinguished Fellow, head of the Structural Biology Center, co-principal investigator at the Center for Structural Genomics of Infectious Diseases, and a corresponding author of the study says that What we discovered earlier this year is that the human and bacterial versions bind differently. This is very important for finding a molecule to build a drug around � you don't want to inhibit a human enzyme, just the pathogen one�.

Until now, scientists have been really interested in knowing the characteristics of the IMPDH enzyme, but unfortunately, most have been unsuccessful in acquiring adequate amounts of it for research analysis.

Joachimiak's team was able to observe that one part of the protein was quite wobbly and unstable, so they opted to modify it without that part using equipment from their Advanced Protein Characterization Facility and then determined the detailed structure of the protein using synchrotron protein crystallography at their Advanced Photon Source laboratory.

The version that they were able to produce has properties that are very similar to the original protein, but it is much easier to purify and crystallize for analysis.

Collaborators from Brandeis University and University of Minnesota Professor Lizbeth Hedstrom and Professor Courtney Aldrich, respectively, who are collaborators of the study, have been able to identify some inhibitor molecules that target IMPDH. These molecules may be a good basis for making a drug, but in the past, they were not able to image these molecules while interacting with the enzyme itself. But because of Joachimiak's modified version, they are now able to take images of these molecules while they are bound to IMPDH.

Another collaborator from the National Institute of Allergens and Infectious Diseases, Helena Boshoff, conducted complementary studies that were able to show that these inhibitors in fact did inhibit the growth of mycobacteria.
The newly discovered structures were deposited into the Protein Data Bank for further study.

To know more about infectious diseases, please feel free to read our other articles on this site.

Written by: Yevgeny Aster Dulla, MSc

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