Drug Discovery

Looking to play videos or audio recordings such as lectures? If you are having trouble playing them try using the free player VLC. It can be downloaded for many types of devices including mobile OS. Links are below:

iTunes

Google Play Store (Android)

PC

MAC

 

RefME is a platform I have talked about before as a useful piece of kit for managing your referencing. RefME has been purchased by another reference manager which has both free and premium (pay to use) versions called Cite this for me. RefME will shut down in due course so it might be worth considering moving to another manager. Cite this for me is a very simple to use reference manager but there are quite a few programs out there which offer both free and premium versions. A list of my top reference managers can be found below:

Zotero has chrome plugins to assist reference capture.

January 2017 Exam Timetables are now available here:

http://www.it-tallaght.ie/examtimetables

The Openstax organisation offer free books that are peer-reviewed by scientists and other academic individuals. There are currently a number of books available by them related to biology but they have now launched a new microbiology book well worth having a read of. It may help you with your studies. You can download the Microbiology book at the link below:

https://d3bxy9euw4e147.cloudfront.net/oscms-prodcms/media/documents/Microbiology-OP.pdf

This image below outlines the step by step process for HPLC Method Development.

Method Development

Courtesy: Researchgate

Agilent has a few nice guides on HPLC which I’ve attached below.

Agilent HPLC Basics

Agilent HPLC Separation Fundamentals

Agilent Rapid HPLC Method Development

Ray D’arcy had Prof. Michael Barry of the NCPE (National Centre for Pharmacoeconomics) on his radio show. Prof. Barry discussed the recent orkambi decision and the role the NCPE has in the national formulary. Really interesting conversation and well worth a listen. The podcast can be downloaded from the link below:

NCPE on Ray D’arcy

One of your colleagues found a very good book on Pharma Science on the web and it’s available free. The title of the book is: Pharmaceutics: The Science of Dosage Form Design 2nd Edition By Micheal E. Aulton and can be found at the link below.

http://bit.ly/pharmascienceebook

Below are two links to sets of videos giving very basic explanations of how various chromatographic methods work.

Chromatographic Methods:

Mr Simple Science:

The link below will take you to a very useful bit of software created using excel that allows you to explore the effects of various parameters on the elution profile of a product. You can play around with column length, elution method (gradient or isocratic), injection volume, temperature and much more and see their effect on resolution and retention time. The first link gives a good overview of the software’s capabilities and the second link is to the program itself which you can download for free and run on PC or Mac.

Among the offered possibilities, it allows you to:

  1. Illustrate the concept of chromatographic resolution including the impact of retention, selectivity and efficiency on resolution.
  2. Understand the van Deemter equation and kinetic performance in HPLC.
  3. Recognize the importance of analytes lipophilicity (log P) on retention and selectivity in reversed phase HPLC mode (RPLC).
  4. Handle the RPLC retention, taking into account the acido-basic properties (pKa) of compounds and mobile phase pH.
  5. Simulate the impact of mobile phase temperature on HPLC separations
  6. Understand the behavior of a mixture of diverse compounds in both isocratic and elution gradient modes.
  7. Show the influence of instrumentation (injected volume and tubing geometry) on kinetic performance and sensitivity in HPLC.
  8. Demonstrate the impact of analytes molecular weight on thermodynamic (retention and selectivity) and kinetic (efficiency) performance.

The website below is a great resource for staying current on topics in relation to liquid chromatography and gas chromatography. Sections of the site include:

  • Publications on LC and GC systems
  • Information on techniques including:
  • LC
  • HPLC
  • UPLC
  • GC
  • Mass Spec
  • Sample Prep
  • LC/GC Television and Multimedia
  • eBooks (Free)

http://bit.ly/lcgcresource

Below is a link to some interesting review papers on HPLC/LC systems. Well worth a read to help you better understand the topic. Explore more on your own by visiting pubmed.gov. Remember to use the filters on the left hand side of the page to help you narrow your searches.

http://bit.ly/hplcpapers

The link below is to a really useful website explaining concisely all the terms used in speaking about HPLC/LC systems. Well worth book marking:

http://bit.ly/hplclcterms

As an update to a previous post on this please note there is a newer and more often updated free desktop publishing software known as Libreoffice. Not everyone has or can afford Microsoft Office but there are plenty of free packages out there that do much the same as Microsoft office and are similarly easy to use. You can get a free office suite of programs from many companies and organisations but one of my favourites is Libre Office. Select the version open office for your system here:

https://www.libreoffice.org/download/libreoffice-fresh/

Medicines manufactured by the pharma sector cost significant amounts of money to go from discovery to market. This can mean that many medicines when they launch are beyond the ability of most people to afford them. In most cases the largest purchaser of pharmaceuticals are countries. Countries buy the drugs for their own national formularies. In an ideal world everyone would get the drugs they need to treat their illnesses. This unfortunately is not the case. Countries have limited budgets with which to buy essential medicines. Pharmacoeconomics is the study of the value of one drug or drug therapy over another. In Ireland the NCPE (National Centre for Pharmacoeconomic Evaluation) takes on the task of deciding which drugs should be made available freely from the state. Their mission is:

…to facilitate healthcare decisions on the reimbursement of technologies, by applying clinical and scientific evidence in a systematic framework, in order to maximise population wellness. The NCPE assess evidence for comparative effectiveness and cost-effectiveness of technologies for use by patients in Ireland. This is done through assessment of evidence submitted by manufacturers and independent systematic review. The NCPE also undertake research to inform national guidelines for health technology assessment.

NCPE

The EMA (European Medicines Agency) which is the EU regulator of the pharmaceutical, bio-pharmaceutical and medical device sector currently has its head offices for all of Europe in London. Following the vote on Brexit, and once the UK follows through on leaving the EU, the EMA will have to fine a new home for it’s HQ in a European country. Ireland may be well placed to become home to the new HQ due to the size of the sector in the country. We’ll have to watch and wait for now.

Below are two videos showing what goes into the process of fermentation, where the cells produce the product (part 1), to product separation and recovery (part 2). These illustrate many of the aspects we are discussing in class.

Below are links (some requiring ITT Dublin library login details for full article access) to interesting articles about the use and potential use of CRISPR/cas9 editing in pharmaceutical bioprocessing. Well worth a read if you’re interested.

 

The impact of CRISPR-Cas9 on target identification and validation (requires ITT Dublin login)

CRISPR-Based Technologies and the Future of Food Science

Accelerating genome editing in CHO cells using CRISPR Cas9 and CRISPy, a web-based target finding tool

Exploiting CRISPR–Cas immune systems for genome editing in bacteria

Small molecules targeting microRNA for cancer therapy: Promises and obstacles (requires ITT Dublin login)

2016-03-18_15-36-09

 

 

Clinical trial details that the US FDA is monitoring can be found at http://clinicaltrials.gov but if you want to see what’s happening in Europe check out http://clinicaltrialsregister.eu The European only launched recently (January 2016).

EU Clinical Trials Register

 

CRISPR/cas9 is a defense mechanism used by certain bacteria to protect themselves against viral (bacteriophage) attach (see figure below). The most commonly used CRISPR/Cas9 bacteria system comes from the bacteria Streptococcus pyogenes. Essentially as the bacteria is exposed to viruses it keeps portions of the viral genetic code (in the form of  short RNA sequences) around so it can recognise the virus again. The CRISPR system keeps a record of the viral genetic code and the cas9 enzyme does the cutting. If the CRISPR/cas9 system encounters a virus it recognises in the bacterium the cas9 enzymes chop up the viral DNA preventing the virus from replication.

Crispr Bacterial Defence

What’s so interesting about this? Well scientists have been able to extract this system from bacteria and use it to quickly and efficiently create transgenic organisms. The system allows for much more precise modification of a genome then traditional methods. Traditional methods of producing transgenic animals has involved injecting genetic material into embryos and hoping for homologous recombination. This technique not only had plenty of failures but also many non specific effects through in correct targeting of the sequence that the scientist wants altered. A successful transgenic animal could take up to a year to produce. With CRISPR/cas9 specificity this can be shortened to as little as 12 weeks. Below are some articles/papers explaining the system.

CRISPR = Clustered regularly-interspaced short palindromic repeats

The Health Sciences department in the University of Utah has a lovely website explaining many aspects of biology and molecular biology through videos and interactive animations. The home page is here : http://learn.genetics.utah.edu/ with lots of links to explore but I’ve put together some of the most relevant pages below.

 

 

The animations below will show you how both PCR and RT-PCR work.

The PCR instructional animation can be found at this link. You can either watch and interact with it on the page or download it for Mac or PC at the links on the page.

https://www.dnalc.org/resources/animations/pcr.html

 

The interactive RT-PCR instructional animation can be found at the link below.

http://www.bio.davidson.edu/courses/Immunology/Flash/RT_PCR.html

Scitable is a website run by Nature Publishing Group which provides biology students with resources on genetics and cell biology. It has great images, explanations (definitions), articles and much much more on everything to do with biology. Well worth checking out if you’re studying for exams or researching for assignments.

http://www.nature.com/scitable

2016-02-23_07-26-24

 

You can have a look around the ITT Dublin pilot plant using the embedded virtual tour below. For a full screen tour click the following link:
http://bit.ly/pilotplant

There’s a Moodle mobile app available for iOS and Android devices. It might be useful accessing information away from your PC/Mac. The apps are available from the links below:

iOS

Android

 

From the BBC website

Reckitt Benckiser, the maker of a range of Nurofen products based on the active ingredient ibuprofen lysine, has been ordered by an Australian court to remove a number of its products, including Nurofen Back Pain, Nurofen Period Pain, Nurofen Migraine Pain and Nurofen Tension Headache, from shop shelves.

The action was taken by the Australian consumer watchdog, Australian Competition and Consumer Commission (ACCC), who argued in court that there was no difference between the different branded drugs used to treat different types of pain but which all contained the same levels of the active ingredient, ibuprofen lysin. The Federal Court of Australia has given the company 3 months to remove the products from Australian shelves.

The move has no effect in other jurisdictions around the world but may prompt further investigations. A spokesperson for Reckitt Benckiser said “Nurofen did not set out to mislead consumers”.

Update: The UK’s Advertising Standards Authority (ASA) is now investigating a number of complaints made against Nurofen about an ad on Nurofen Express. Similar complaints are being investgated in New Zealand too.

RefME is a free reference manager. It can help you capture references on the web and put them together into file format you can export and use in your thesis submission or project submission. For some general info on how it works and what it’s compatible with see this earlier post on LectureHub here. The video below will show you how to capture references on ncbi.nlm.nih.gov/pubmedbiopharminternational.com and books.google.ie to start with but it can do so much more. Well worth considering using it to help you with your thesis/essay writing.

RefME is a free reference manager that works as an add-on to a desktop browser and also as a mobile app. It is available as an app for iOS and Android. With the apps you can scan barcodes of books or search for references and then add them to your account.

It also works with Google Chrome Browser. This app and browser plugin will help you capture (from pubmed or any other web page where you have a potential reference) and manage references to go into your thesis. Once you’ve captured your references and used them in your thesis you can then export all references in the proper format (Harvard is probably the best format) and copy and paste them into your thesis.

You can sign up with a google or facebook account plus it’s completely free. More info can be found at the link below and I’ll put together a short video on how to use it later this week.

http://the12appsofchristmas.zohosites.com/App7.html

If you’re looking for past papers for any subject you are studying you can get them from the ITT Dublin Library website at this link:

http://millennium.it-tallaght.ie/search/r

 

 

The ITT Dublin Library has an agreement with openstax college who have made available a number of free books covering many subjects.

The full list of books can be found here:

https://www.openstaxcollege.org/books

I have reviewed the Biology, Microbiology and Concepts in Biology books and think they are all well written and applicable to the course. If you need to read extra material to help you understand your notes I can wholeheartedly recommend them. If you’ve any queries just give me a shout.

Biology:

http://0-openstaxcollege.org.millennium.it-tallaght.ie/textbooks/biology

Concepts in Biology:

http://0-openstaxcollege.org.millennium.it-tallaght.ie/textbooks/concepts-of-biology

Microbiology:

http://0-openstaxcollege.org.millennium.it-tallaght.ie/textbooks/microbiology

Chemistry:

http://0-openstaxcollege.org.millennium.it-tallaght.ie/textbooks/chemistry

Polymixins are a type of antibiotic of which Colistin is one. Polymixins and in particular colistin are one of our last lines of defense against serious bacterial infection. While resistance has been seen against these antibiotics it has only occurred through mutations in the chromosome of the bacteria making resistance difficult to pass on to other bacteria. A new research article in The Lancet Infectious Diseases has reported that, for the first time, resistance to colistin has been detected on a plasmid. This is of significance as bacteria can transfer/share plasmids readily and thus spread resistance much more quickly then through mutations in the chromosome.

This raises the real possibility of the emergence of untreatable diseases. Are we at the beginning of a new era of bacterial superiority?

http://www.bbc.com/news/health-34857015

Once a patent expires for a drug (after 20 years) other manufacturers will step in to start selling the same drug but marketed as a generic. A recent investigation by skynews reported that the differences between some of these generic drugs (specifically pain killers) and their branded equivalents were few and far between.

…consumers in the UK are spending more on painkillers than ever before, a Sky News investigation reveals branded pills that claim to target pain can cost up to four times more than unbranded tablets…Jayne Lawrence, professor of biophysical pharmaceutics at Kings College London, said: “Some people believe that by taking a more expensive preparation, perhaps a branded formulation, they’ll get better pain relief.

“If it’s the same dose of drug, in the same formulation, the customer will experience no difference.”

Courtesy Skynews

The links below describe in detail how to use either Harvard or Vancouver referencing styles for writing an essay/thesis. Harvard is probably the easier to use especially if you don’t have a reference manager program. This is due to the fact that it is very forgiving if you need to add additional detail to the article. Instead of having to re-number ever reference if you used Vancouver style, you can just add the surname and year to the new reference and just put the references in alphabetical order at the end of the article.

The most important thing to remember with referencing is to be consistent with what ever style you use. Use of web links is never appropriate for referencing!

IT- Tallaght

Harvard Style

Guide to Writing Styles and Citing Sources

 

UCD

Harvard Style Guide

Vancouver Style Guide

Not everyone has or can afford Microsoft Office but there are plenty of free packages out there that do much the same as microsoft office and are similarly easy to use. You can get a free office suite of programs from many companies and organisations but one of my favourites is Open Office. Select the version open office for your system here:

https://www.openoffice.org/download/index.html

The link below is to an article exploring “Antibiotics and Bacterial Resistance in the 21st Century”. It’s long but it’s an interesting read. Not essential for any exams but a worthwhile read anyway.

Antibiotics and Bacterial Resistance in the 21st Century

Peer reviewed material is material published in scientific journals (or other types of journals). These articles have been published in these journals only following review of the articles by other scientists who assess the quality and validity of the material.

News articles and websites are not peer reviewed and anyone can right anything there whether it is true or not. In scientific essays you should focus on referencing peer reviewed material first and foremost before utilising other material.

Sample paragraph showing multiple references:

“TLR3 recognizes viral dsRNA and endogenous dsRNA derived from necrotic cells during inflammation (11, 12). In humans, defective TLR3 function has been associated with enhanced susceptibility to viral infection and in particular, herpes simplex encephalitis (13). Recently, a functional TLR3 polymorphism, Leu412Phe (TLR3 L412F, rs3775291) was described which results in attenuated NF-B- and IRF3-signaling in affected cells (14). TLR3 412F has also been shown to confer protection against geographic atrophy in macular degeneration by attenuating TLR3-induced retinal epithelial cell apoptosis (15).”

References should be used throughout the essays. The above piece is in Vancouver Style. Other referencing styles can be found here. Details of what Vancouver style is and how to use it for different types of references can be found here:

Vancouver Style

Plagiarism includes:
  1. Using another author’s words without proper citation
  2. Using another author’s ideas without proper citation
  3. Citing a source but reproducing the exact word without quotation marks
  4. Borrowing the structure of another author’s phrases/sentences without giving the source
  5. Borrowing all or part of another student’s paper
  6. Using paper-writing service or having a friend write the paper

Avoid using significant amounts of quotes to in your essay as this is not appropriate. Put things you’ve read and understand in to your own words.

Vaccines

A vaccine is a biological preparation that improves immunity to a particular disease.Whether that’s a disease caused by a bacteria or a virus.
 
Antibodies

An antibody (Ab), also known as an immunoglobulin (Ig), is a large Y-shape protein produced by plasma cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, called an antigen.
 
Cytokines

Cytokines (Greek cyto-, cell; and -kinos, movement) are a broad and loose category of small proteins (~5–20 kDa) that are important in cell signaling. They are released by cells and affect the behavior of other cells, and sometimes the releasing cell itself. Cytokines include chemokines, interferons, interleukins, lymphokines, tumour necrosis factor but generally not hormones or growth factors (despite some terminologic overlap). Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell.
 
Hormones

A hormone (from Greek ὁρμή, “impetus”) is a class of signaling molecules produced by glands in multicellular organisms that are transported by the circulatory system to target distant organs to regulate physiology and behaviour. Hormones have diverse chemical structures that include eicosanoids, steroids, amino acid derivatives, peptides, and proteins. The glands that secrete hormones comprise the endocrine signaling system. The term hormone is sometimes extended to include chemicals produced by cells that affect the same cell (autocrine or intracrine signalling) or nearby cells (paracrine signalling).
 
Gene Therapy

Gene therapy is the use of DNA as a drug to treat disease by delivering therapeutic DNA into a patient’s cells. The most common form of gene therapy involves using DNA that encodes a functional, therapeutic gene to replace a mutated gene. Other forms involve directly correcting a mutation, or using DNA that encodes a therapeutic protein drug (rather than a natural human gene) to provide treatment. In gene therapy, DNA that encodes a therapeutic protein is packaged within a “vector”, which is used to get the DNA inside cells within the body. Once inside, the DNA becomes expressed by the cell machinery, resulting in the production of therapeutic protein, which in turn treats the patient’s disease.

 

Stem Cells

Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells. They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm, endoderm and mesoderm (see induced pluripotent stem cells)—but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.
 
Blood Products

A blood substitute (also called artificial blood or blood surrogates) is a substance used to mimic and fulfill some functions of biological blood. It aims to provide an alternative to blood transfusion, which is transferring blood or blood-based products from one person into another. Thus far, there are no well-accepted oxygen-carrying blood substitutes, which is the typical objective of a red blood cell transfusion; however, there are widely available non-blood volume expanders for cases where only volume restoration is required. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovah’s Witnesses and others who have religious objections to receiving transfused blood.

Taken from Wikipedia

The website Pharmacology Corner looks to me to be a great resource for drug discovery, targets and receptors information. Well worth checking out to help with your studies and essays.

2014-09-30_11-49-41

The image below shows the effect of agonists and antagonists on a biological reaction. In figure “A” the agonist alone causes a reaction but add the agonist and competitive antagonist this changes the reaction. You now need more agonist to get the same effect (this is competitive antagonist). In figure “B” you see again the effect an agonist has on a biological reaction but when we add the agonist together with a non-competitive irreversible antagonist we see the effect is to reduce the rate of the reaction.

 

competitive-antagonist

 

Courtesy: Pharmacology Corner

The image below is a detailed description of the HIV virus life-cycle and the targets in this life-cycle we can use drugs on. Click the image to see the full size pic.

 

2007 aids

The image below is from the article Steroid hormones: Interactions with membrane-bound receptorsIt shows three ways that a steroid hormone (drug) can interact with a cell. (a) The classical model. The steroid hormone dissociates from its plasma carrier protein and diffuses across the cell membrane. After gaining entry to the cell, the free hormone binds to an intracellular receptor and alters gene transcription. (b) Receptor-mediated endocytosis. The steroid hormone, bound to its plasma carrier protein, is brought into the cell via a cell-surface receptor. The complex is broken down inside the lysosome, and free steroid hormone diffuses into the cell, where it subsequently exerts its action at the genomic level or undergoes metabolism. (c) Signalling through cell-surface receptors. The free steroid hormone alters intracellular signalling by binding to cell-surface receptors. The steroid hormone could exert these effects directly or could alter signalling by blocking the actions of peptide hormones.

 

gr1

The links below are to resources you can use which will help you with your literature surveys/essays or studies in general.

ITT Dublin Library Medscape
The Cochrane Library Google Scholar
National Library of Medicine Web of Science
Google Books FDA
Clinical Trials HPRA
Biocheminternational  PharmaTech

 

This is advice taken from Carlton University in Canada from their department of economics but it is very useful in general for writing academic essays.

Academic Essay Writing

The link below is a sample 1500 word essay from the University of York which contains also tutor comments on the layout and structure of the students essay. Well worth a read for your own studies.

Sample 1500 word Essay on referencing

Research papers are a great resource for learning. One of the largest databases of peer reviewed published research papers is housed by the US National Library of Medicine National Institutes of Health. You can find specific papers on techniques or new discoveries or review papers which offer a broad look at a particular topic. This should be your first stop for research on topics we’re discussing in lectures or for your assignments.

http://www.ncbi.nlm.nih.gov/pubmed/