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Automation in High-throughput screening
Posted on February 5th, 2010 No commentsDrug discovery uses the major amount of its resources for the high throughput screening. Based on specific probabilistic calculation, large experiments in HTS are performed by pharmaceutical and biotech companies to identify some molecules that could become drug after further long analyses. Robots are usually used in this complex process. It’s important that all data are generated in reliable and accurate manner in order to obtain useful results.
Robots can execute some passages: from serial dilution to reaction buffer disposal. In each of these steps, errors could be generated and, giving the small volumes in which HTS is usually performed, robots must be well calibrated in order to exclude the possibility to have this kind of problems. A lot of data arises from an HTS. Data management and statistical analyses are other key- steps for the high throughput screening. Thus, IT systems have not only to control robots to correctly work, but also help scientists to produce meaningful results from raw data. This kind of experiments are highly expensive and can be repeated only strictly necessary times. However, it’s really important to plan the experiment in the correct way and set up robot ant other IT systems involved into the process to obtain more data as possible. -
Sperm cooperates to fertilize an egg
Posted on February 3rd, 2010 No commentsRecent studies published this week on Nature journal demonstrated that sperm can link up with other cells in order to swim faster and successfully reach the egg. Surprisingly, scientists from Harvard University noted that sperm form clusters only with cells of relatives.
They labelled sperm with fluorescent probe and published fantastic pictures in which clusters were colored with only one color. This means that cluster was formed by sperm derived from one male. From a biological point, in species in which female copulates with several males before getting pregnant sperm helps itself to promote mate generation. It seemed that some genetic information could help on this process. Sperm recognizes its relatives through a sort of fingerprint, it’s not only for spatial opportunity that sperm link with its similar that presumably enters and are in the reproductive tract at the same moment. Next step will be to understand which is the genetic basis undergone to this interesting process and evaluate if the same behavior could be identified also in human beings, keeping in mind of course that female usually doesn’t copulate with several males to get pregnant. Indeed, some fertilization treatment could be created on the basis of this study. -
New challenges for synthetic biology
Posted on February 1st, 2010 No commentsSynthetic biology is a modern discipline that tries to manipulate cells and program them to perform some activities useful for us. Different products or services may be provided by cells, for instance production of biofuel or toxin identification into a body as well as controlled insulin release. Synthetic biology requires a strict control of the system, but many parts involved into the process have not been known yet.
For instance, DNA sequence in the promoter region is not always well characterized and this is a crucial point to increase cell productivity. So, the first point to be clarified to obtain results from synthetic biology is the knowledge of expression system. Furthermore, it’s important to understand how all parts can work together. This is another challenge for synthetic biology because of the complexity of regulation mechanism into the cells. Circuits can work in an unpredictable manner and results are often few understandable. Finally, even if the circuit seems to work very well, the system could not be reliable in all situations and it could fall because of genetic mutations which could arise in any time. In summary, synthetic biology is an important challenge for scientists for the next future. Biofuel, toxin detection and insulin release are only three of different purposes for which this discipline must be applied. -
Statistics in science
Posted on January 29th, 2010 No commentsA common English quote says that there are three kinds of lies: lies, damned lies and statistics. This sentence was wrongly attributed to Disraeli, whereas it was firstly published by Marc Twain. Even if it could seem true, statistics is the only tool available up to date to manage a large amount of data and to give their a mean. Several functions are usually used in statistical analysis; the most common are the average, standard deviation, frequency and also the number of observation is reported in scientific publications.
All these data are defined as descriptive statistics because of their direct characterization of the population of interest. In other cases more complex calculations must be done to find significance from the study. Linear or logistic regressions are models to identify the trend that better explain and summarize the collected data. From linear or logistic regression is possible to interpolate or extrapolate data in order to predict results into the studied range or outside the studied range, respectively. Furthermore, from statistical analyses prevalence, incidence, absolute risk, odd ratio and relative risk are determined. All of these parameters are so important that must be determined during clinical study and are subsequently used to compare different protocols, drugs and so on. Clinical studies are classified as experimental studies or observational studies. The main difference between these two classes is the presence of a treatment given to patients in the experimental studies, whereas in the observational studies none treatment is followed but the selected population is just observed to determine the parameters of interest. In both cases, given the high number of patients enrolled in order to obtain significant results, statistics is useful to compare treated cohort and placebo cohort, for example, as well as to evaluate the role of specific component of the study, namely called covariates.
The major part of software that help to collect and manage data from a clinical study have also some algorithms to calculate standard statistical parameters during the data collection self. Revision and further elaboration must be done by professionals in order to correctly consider study results. Statistics is important not only in clinical trials, but also in all experiments performed in science. Indeed, to be sure to have obtained a result as a consequence of certain conditions and not due to serendipity, all experiments are usually repeated three or more times. Data presentation normally comprises average and standard deviation or confidence interval and significance is determined by a series of tests that should be described in material and methods section of the publication. In conclusion scientists must have some basis of statistics because this discipline confers value to their experiments and make them shareable and comparable with scientific community. Even if statistics is considered as a lie in some cases, it will be useful for science advances. -
The pediatric knowledge base
Posted on January 25th, 2010 No commentsThe pediatric knowledge base (PKB) is an IT system developed at the Pediatric Pharmacology Unit of the Children’s Philadelphia Hospital. This project involved professionals from several disciplines, such as medicine, pharmacology, statistics, bioinformatics. They built a model in which clinical data from patient were combined with electronic medical records and drug profiling, in order to obtain an IT tool able to continuously learn information about the patients self.
PKB helps physicians to choose the better pharmacological therapy in terms of dose, agent performance, collateral effects and drug combination. Based on the profile of three common drugs, such as vancomycin, methotrexate and tacrolimus considered as prototype, PKB monitors the drug use and helps to predict the outcomes in children patients that are often more difficult to treat. PKB is updated by numerous hospital members, in this way deep knowledge about clinical adverse events or clinical advantages as well as innovative protocol can be shortly acquired with great benefits for patients. Furthermore, PKB is web based and it could be shared between hospitals of different countries. A consortium is planning to be created to coordinate PKB implementation across the world. Using PKB as a model, it could be possible to set up similar dashboard for other class of patients in the next future. -
The role of IL10 in autoimmunity
Posted on January 20th, 2010 No commentsSeveral immune diseases seriously compromise life quality of patients and cause important deficit in general body functions. One common autoimmune disease is the Insulin Deficient Diabetes Mellitus (namely IDDM) which arises during childhood and often correlates with autoimmune response versus pancreatic islets. Transplantation is the best treatment for this kind of disease, but is possible only in presence of a compatible allotype and also in this case the possibility to have a rejection is quite high. Immune suppression and other similar approaches have been optimized to bypass this problem. For this purpose, since few years the role of dendritic cells in autoimmunity control has been investigated. In particular, when dendritic cells were modified by inserting IL10 gene and injected into kidney mouse model, T lymphocyte proliferation was inhibited and apoptosis was induced, glucose plasma levels were downregulated and returned to normal value. In general, IL10 transfection generated a favourable tolerance of islet graft and prolonged survival of recipients by inhibiting T cells proliferation. Other studies must be done about the role of IL10 in autoimmunity and signalling pathways involved in this process. The final goal is totally decreasing the likelihood to have rejection after transplantation and making possible this treatment also in the case of not complete compatibility between donor and host.
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Immune system involvement in TB
Posted on January 18th, 2010 No commentsTuberculosis is one of the diseases eliminated from occidental countries, even if few cases are reported every year. Granuloma formation into lung is the fundamental characteristics of this disease and the involvement of our immune system in this process is argued since long time. In advance of publication number of Cellular and Molecular Immunology an important paper illustrates how our immune system has a consistent role in granuloma formation and which kind of T cell are involved.
The comparison between blood samples derived from Tuberculosis patients or healthy donors demonstrated that the presence of a special group of T cells – namely the IL 17 producing γδ T cells- in peripheral blood was significantly higher in patients than in healthy donors. In vitro re-stimulation with tuberculosis mycobacterium antigen generated an increase in IFNγ producing T cells ratio in patients than in healthy donors, while the ration of IL17 producing cells was similar within two groups. These data were consistent with other results obtained in mouse model and confirmed the role of IL17 in granuloma formation. The identification of γδ T cells as major IL17 producer may arise some advantages for possible pharmaceutical treatment, but further elucidations are required to better understand all the mechanism at the basis of this complex disease. -
IT system protection
Posted on January 15th, 2010 No commentsThe broad diffusion of technologies such as computers, databases, mobile phones and so on, has determined a considerable change in our life. We usually use this kind of instruments at the work or school, at home and in other situations of everyday life.
It’s really important that the global IT system would be safe and protected from hacking attacks. Last year, an important mobile phone manufacturer company found vulnerability in its system and phone calls could be listen by everyone knew this failure. This first episode started an intensive research on security system in order to preserve IT and our privacy. Scientists were called to identify flaws into algorithms, acting like legal hackers, and were invited to share their skills and experiences with the community. So, manufactures changed their habits to reject the possibility to reveal flaws in their systems and choose an ethic approach to improve the worldwide knowledge. Also manufacturers that produce IT systems for pharmaceutical companies must consider the opportunity to look for new devices to protect all sensible data regarding the clinical study. Indeed, personal details of patients contained in clinical study are usually shared between centres involved in the trial and become more sensitive of possible attacks. Thus, it’s ethic that these data should be preserved. -
Tetracycline derivative can modulate SMN expression
Posted on January 12th, 2010 1 commentSurvival of motor neuron centromeric (SMN) genes are involved in spinal muscular atrophy when mutated. This disease is an autosomal recessive disorder that progressively determines the loss of spinal alpha motor neurons, causing death during the childhood.
Deletion in SMN1 gene generates a truncated protein without functionality. In a similar situation another protein of the same family SMN2 is produced in larger amount, but this spliced form is unable to overcome the loss of SMN1 and restore its normal activity. SMN2 lacks an exon (7) important for protein function, this is the reason for which SMN2 cannot completely restore SMN1 activity. Researchers observed that tetracycline derivatives could interfere with splicing mechanism and promote the inclusion of exon 7 into SMN2 mRNA. They identified the less toxic ones in order to modulate SMN2 expression without collateral effects. Rather than the toxicity, the second problem that researchers had to solve was the blood brain barrier crossing because tetracycline derivatives cannot cross this barrier. Scientists proposed firstly an injection into brain, then the use of osmotic pump to internalize these useful drug in SMA patients. Giving the lethality of this disease, it’s important that all routes are checked and considered in order to find the right one. -
Increased incidence of cardiovascular diseases during holiday
Posted on January 8th, 2010 No commentsChristmas is one of the most magic moment during the year and New Year’s Eve is really exciting. Nevertheless, some studies reported in literature demonstrated a correlation between heart attack and winter holiday. It could sound strange because stressor elements that have an important role in heart failure should not be present during holiday.
Anyway, other stressor components can be listed during Christmas celebration such as forced relationship with relatives, financial efforts to purchase gifts, travelling expenses. In addition to these components, during holiday overindulgence in diet usually occurs: indeed, major intake of salt, fat and alcohol can contribute to cardiovascular problems. We must remember that the cold season itself determines an increase in cardiovascular diseases due to a natural increase of vascular resistance and probability to have thrombus formation and coronary spasm. Furthermore, a happy atmosphere could determine a delay in seeking medical attention that could resulted as fatal. In general, physicians try to instruct patients with high risk factors to recognize heart attack at the beginning in order to look for medical care as soon as possible. Relatives of patients must be informed about the increased likelihood to have cardiovascular problems during holiday.
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