Stem cell sharing – part 2

Last week, I wrote about my experience of being a potential stem cell match for someone suffering from leukaemia or other blood disorder. Today, I’ll explain how someone is a “match” and the technology used to test this.

The theory

The surface of every cell (except red blood cells) is decorated with a cluster of proteins known as the major histocompatibility complex (MHC). In the event of infection, the invader (pathogen) is chopped up and parts are stuck onto the MHC. This serves as a signal to immune cells that a response is required. For example, if a cell is infected with a virus, parts of the virus are displayed. An immune cell known as a killer T cell will come along, recognise the MHC with added viral fragment, and pass a signal to the infected cell to shut down and die to slow the advance of the invading horde!

If cells from another human are encountered by the immune system, a difference in MHC tells the immune system that the cell is foreign and an immune response is mounted. This is an understandable response; it’s what defends us from infection but is exactly what we don’t want to happen in a transplant scenario. Stem cell transplants are even more complex as the cells go on to produce the immune system. These could go on to attack the recipient’s existing cells in what is known as graft vs host disease.

To avoid this rejection of cells from other people, we need to pick the donor correctly and it all comes back to the MHC. We need the MHC of donor and recipient to be as similar as possible to give the best chance for the cells to accepted, and in the case of stem cell transplant, avoid graft vs host disease.

The practicalities

How do you go about testing the compatibility of donor and recipient? We need to compare the proteins that make up the MHC in the patient and all the donors on our registry.

My former lecturer has a memorable saying about biochemistry: “DNA is easy, protein is fun“. What Dr Cox means by fun is that working with proteins is difficult, unpredictable and frustrating compared the the simplicity of dealing with DNA.

Fortunately, we understand that proteins are the products of genes, which are comprised of DNA. Here’s a reminder of the central dogma.

DNA –> mRNA –> Protein

By comparing the genes that code for the MHC, we can compare the nature of the proteins. The genes considered important for matching are: HLA-A (1,833), HLA-B (2,459), HLA-C (1,507), HLA-DRB1 (1,047), HLA-DRB3 (46), HLA-DRB4 (8), HLA-DRB5 (17), HLA-DQB1 (337) and HLA-DPB1 (205). They are named HLA after Human Leukocyte Antigen, another term for the MHC. The numbers in brackets indicate the number of protein variants known in January 2014 (source).

As you can see, there are lots of different versions of the proteins and the chances of any two unrelated people being a match is low.

The technology

(The following is based on information from Anthony Nolan. I don’t know what techniques other registries use but they are likely to be similar.)

One benefit of carrying out analysis on DNA is that we know how to amplify it. We can take the enzymes used to replicate DNA in bacteria and use them for our own purpose of replicating DNA in a plastic tube! This technique is called polymerase chain reaction and is one of the fundamental techniques of molecular biology. It is to DNA what a photocopier is to information on a sheet of paper. Kary Mullis won the Nobel Prize for inventing this process. Once DNA is amplified, we have lots of copies to do testing on.

All samples from donors and patients are tested using a very clever fluorescence technique. Many, many different synthetic DNA molecules are attached to lots of tiny fluorescent beads. Each bead has a unique colour and is decorated with only one type of DNA. Elsewhere, the amplified DNA from the humans is labelled with a fluorescent molecule of a different colour. If the synthetic DNA and DNA from the human being tested are similar, they will stick together, known as hybridisation. Each bead is then looked at by a computer controlled microscope that identifies the colour of the bead, and if DNA has stuck. If you want more information about this remarkable machine, check out the product website. This method is used as a primary way to identify the type of MHC of the patient and potential donors, however it only gives a rough idea of similarity as DNA will still hybridise if there is a small difference.

This shows that the subject has DNA similar to the DNA immobilised on the cyan bead.

This is the technique used to test all donors and patients. Next week, I’ll talk about how higher resolution matching is achieved.

If you’re hungry for more information or interested in joining a stem cell registry, I hope these links to UK organisations will satisfy you.

BBMR – Blood donors can join at next session if aged 18-49.

Anthony Nolan – People aged 16-30 can join.

DKMS – Accept people aged 17-55 (only 18+ called to donate).

If you’re in another country, take a look at this extensive list of stem cell registries from reddit.

This post is composed of my own views and opinions and not those of the above organisations.

Stem cell sharing – part 1

Some years back, I joined the British Bone Marrow Registry. It was a simple process, just an extra sample was taken during a blood donation session. A card with my registry ID number has sat in my wallet since then and I’ve thought little of it.

Last week: I received a letter from the BBMR saying I am a potential donor for a patient, likely someone suffering from leukaemia (leukemia for those in the US) or other blood disorder. Included was a booklet all about the process from Anthony Nolan.

The booklet from Anthony Nolan. It’s a more in-depth version of this page.

I made a quick phone call to answer some health questions, and an appointment at my doctor’s surgery for a blood sample. A week later, I went to the nurse with the sample kit the BBMR posted out to me. After 2 minutes of painless blood sample collection, we packed up the tubes in a Special Delivery bag and I went for a coffee while waiting for the Post Office to open. The samples were destined for Anthony Nolan labs in London indicating the level of cooperation between the different registries.

Packaged samples and the edge of a flat white coffee

It will take up to 8 weeks for the testing procedures to be carried out to find the best match for the patient. Only then will I discover if I’ll play any further part in the process.  What is the process?

There are two ways that stem cells can be collected:

1. Peripheral blood stem cell (PBSC) collection. The donor is given injections of a protein called granulocyte colony-stimulating factor (G-CSF) on 4 or 5 consecutive days. This signals to the bone marrow to make more haemopoietic (blood-making) stem cells which are released into the blood.  The donor is then hooked up to a machine and blood is removed, centrifuged to extract the stem cells and returned in a process known as apheresis. This is the most common method of stem cell donation; ~90% happen this way.
2. Bone marrow extraction. Bone marrow is extracted directly from inside the hip bone (the iliac crest for the anatomists out there).

The choice of method is down to the donor but doctors will advise what is best for the recipient. My preference would be PBSC collection.

Regardless of the source, the collected cells are then transported to the recipient and given intravenously. The patient will have been prepared for this beforehand with strong chemotherapy and/or radiotherapy for three reasons:

1. To destroy existing, faulty bone marrow.
2. To destroy cancerous cells.
3. To weaken the immune system to reduce the chance of rejection of the stem cells.

(source)

Cells will then travel into the bones, form the bone marrow and start producing healthy blood cells. This process is known as engraftment.

My thoughts:

1. As a biochemist, it’s exciting to be part of a real life biotechnology meets medicine situation. I’ve enjoyed reading about the technology Antony Nolan use to match donor and patient.  The development of peripheral blood stem cell collection as a more pleasant method of donation and perhaps more effective treatment for patients (source) is the product of the work of biotechnologists (to produce and purify G-CSF), biomedical engineers (to design apheresis machines) and clinicians (to treat and monitor donors and patients).
2. On a human level, I know there’s someone out there that needs some stem cells and I could be the person to provide them. I find it easier to understand the biochemistry and immunology involved than process this. Whatever the level of my involvement, I wish them all the best. I hope that a small amount of donor discomfort and disruption leads to a healthy life for the recipient.

Check out my whistle-stop tour of finding a match in part 2!

If you’re hungry for more information or interested in joining a stem cell registry, I hope these links to UK organisations will satisfy you.

BBMR – Blood donors can join at next session if aged 18-49.

Anthony Nolan – People aged 16-30 can join.

DKMS – Accept people aged 17-55 (only 18+ called to donate).

If you’re in another country, take a look at this extensive list of stem cell registries from reddit.

This post is composed of my own views and opinions and not those of the above organisations.

Grip Mod for Logitech iPad 2 Keyboard

Happy New Year!

One of my Christmas/birthday presents this year was a Logitech iPad 2 Keyboard. Connects by bluetooth, acts as a stand and makes it much more pleasant to write on. One downside is that it is a little slippery on the underside. It tended to move around a lot on a recent coach journey. Here’s a cheap fix!

I bought some self-adhesive neoprene tape (10mm wide and 2mm thick), cut two ~17 cm strips and stuck them on.

No more slippage! Just need to decide what to do with the remaining 9.6 m of tape…

Bells and whistles in medical technology

At the recent Medtech Motions OBR event, Ian Oliver from Ernst & Young gave an overview of the current field of medical technology.

The idea of medtech companies offering stripped down versions of their devices with reduced functionality but at a lower price was discussed. Emerging markets are sensitive to price and healthcare providers in established markets aren’t exactly carefree when exercising their cheque books.

This made me realise that two types of development are going on in medtech companies:

1. We have people extending existing technologies and creating new ones. This can be guided by immediate needs of patients and practitioners, or be a little more speculative. One example of this is my friend developing new programs for MRI scanners to see processes in the body that are currently hidden (he’s doing this in a university but a medtech company is part-funding the research by providing cheap equipment and will eventually buy the technology).

2. There are others looking to remove superfluous bells and whistles from the device, guided by practitioners. They are also looking to economise on the manufacture of the device by reducing material and labour costs. This McKinsey report tells a good story of a “teardown” exercise where a company compares its device against that of the competition in minute detail.

I believe that the relative efforts put into the two processes above could tell a great deal about individual device markets (scanners, monitors etc.), whole companies and the industry as a whole.

Zopa’s seventh birthday

Early March brought the birthday of the peer to peer finance company Zopa. There was good news from CEO Giles Andrews as accounts released later this year will show a profit! 2012 has seen an increase in applications from borrowers and more loans are being disbursed each week than ever before.

This post serves to explain the Zopa basics.

I’ve been a member of Zopa since late 2006 when they gave me £30 to try it out. After seeing the results of this test I went in with some of my own funds in the middle of 2008.

What is Zopa?
The concept is simple. Zopa links those who want to borrow with those who want to lend. Zopa is a marketplace.  Since its birth over £185 million of loans have been arranged and only 0.9% of this has gone into default. It has won Moneywise’s ‘Most Trusted Personal Lender’ for the past two years. Lenders are making 6.2% per year on average after fees and before bad debt. Borrowers are receiving market-leading rates. Zopa accounts for 1-2% of the personal loan market.

How does it work?
1. Lenders set their desired rate and how much to lend to each borrower. Zopa give predicted bad debt rates and an indication of how competitive your offer is.
2. Potential borrowers apply and Zopa credit check them and give them a risk rating. They are then given a rate based on what lenders are currently offering.
3. If borrowers like the rate, they continue with the application. Zopa continue with credit checking.
4. A few days later, a final decision is made. If approved, borrowers receive the funds shortly after.
5. Repayments are returned to the lender to either withdraw or lend out again.

This sounds risky, what protection is there?
Zopa credit check all applicants and only prime borrowers are accepted. Should a borrower stop making repayments, Zopa deal with chasing. They also manage all the court business if it comes to it. Lenders can protect themselves by only lending a small amount to each borrower to minimise the effect of defaults. Newcomers needn’t lend more than £10 to each borrower!

How does Zopa make money?
Zopa charges a fee to borrowers when they are approved for a loan. There is no early repayment fee, which is quite a bonus for borrowers. Zopa also charge lenders 1% p.a.

My thoughts
Zopa was the first peer to peer  finance operation and I’m delighted to hear that it’s profitable. The timing of its launch was extremely lucky; sufficient reputation was build up when the financial crisis hit and the wave of anti-bank feeling certainly helped get media attention. The fact that Bank of England policymakers are talking about it makes me think disintermediated finance is hitting the mainstream in 2012.

Why not give it a try today? Sign up here and be part of the finance revolution.

 

 

Crowdsourced and gamified innovation from Marblar

This week I have been fascinated by a new website called Marblar. Inventors give details of a new technology and participants give suggestions for applications and improvements. Rewards are offered for the best ideas that come in and one metric for quality comes via upvotes and downvotes from other members. I can’t wait to hear the results of the first rounds of brainstorming.

This reminded me of James Gardner’s Sidestep & Twist where he states that companies must employ strategies for driving innovation internally and a suggestion box simply isn’t good enough. You have to agree and Spigit (where Gardner now works) provides a platforms for ideas to be voiced and evaluated across an organisation.

There are similarities between Spigit and Marblar but there is a difference in the nature of the crowd. Spigit enables a preexisting crowd in the form of a company whereas Marblar has assembled (and will go on accumulating) users to work on problems.

Back to Marblar, two very different technologies are up for discussion at the moment; a novel chemistry for linking DNA and RNA, and electricity generating pedals. Why not pop along to and have a go?

No Cell is an Island – What I Do All Day (Part II)

Ages ago I wrote about how the molecules that cells need (or need to get rid of) travel through the membrane. Now it’s time to consider the problem of transmission of information through the barrier.

First of all we should consider the type of information that a cell receives.

• Hormonal signals e.g. insulin. This is released from the pancreas when blood sugar levels are high. It mainly acts on liver and muscle cells causing a increase of uptake of glucose and subsequent storage as glycogen within the cells.
• Neurotransmitters e.g. acetylcholine. This is released from nerve cells and makes skeletal muscles contract. It also released into the synapase or between two nerve cell, transmitting the signal from one to the other.
• “Environmental conditions” e.g. glucose. Bacteria are able to swim in the direction of increasing glucose concentration. The process of moving in a certain direction based on chemical signals is known as chemotaxis. Also, we can smell all sorts of different chemicals.

There are other classes too but these are the main types that I want to consider today as they illustrate the different mechanisms across membranes but also reinforce the fact that mechanisms are shared across a wide range of different functions.

A key, take home point is that every molecular signal has a receptor. This is a protein that binds the signalling molecule and then passes the message on to the rest of the cell.

Some signalling molecules are able to move through the cell membrane independently. These are generally lipophilic (lipid loving) hormones such as testosterone and cortisol. Once inside the cell, an intracellular receptor binds the hormone and a message is passed down a chain of more proteins until an effector protein is activated causing a response. This doesn’t really involve the membrane so this is as much as I’m going to say about this!

Most hormones and “environmental signals”, and all neurotransmitters bind their receptors at the cell membrane – the receptors are membrane proteins.

One way of getting a message across is through dimerisation, the coming together of two proteins which serves to bridge the inside and outside of the cell. Binding of the signal outside causes two proteins to interact and transfer chemical groups. This changes the structure and allows the binding of further “downstream” proteins and the signal is passed down a chain until the effector is reached. Insulin receptors are believed to act like this, leading to effects such as increased production of glucose transporters.

Another mechanism for signal across a membrane is to activate a enzyme that catalyses the production of a so called “second messenger”. One very large family of proteins that do this are called G-protein-coupled receptors (GPRCs). These bind the signalling molecule, change shape and activates G-protein allowing it to interact with other membrane proteins including adenylate cylase (which makes a chemical known as cAMP), phospholipases (which break apart membrane phospholipids) and ion channels (which allow the flow of ions into the cell). These secondary chemical then diffuses through the cell where it binds other proteins to cause effects. Smell sensors or olfactory receptors are GPRCs!

The final mechanism I’ll talk about today are ligand-gated ion channels (LGICs). These channels open in response to the direct binding of a chemical to the channel such as a neurotransmitter. Binding of acetylcholine to receptors on a muscle cell opens the channel and allows the exit of potassium ions but a much greater entry of sodium ions. This changes the electrical properties of the membrane opening voltage gated calcium channels, causing the muscle fibres to contract. Magic, and not possible without membrane proteins!

Webank One Year On – A Grower, a Silence and a Disappearance

On 21st January 2009 I headed to NESTA HQ to attend their Webank event. A thoroughly enjoyable evening where we heard from 3 companies followed by a discussion panel featuring Giles Andrews from Zopa, James Gardener of Bankervision fame and Umair Haque from Havas Media Lab, chaired by Christian Ahlert from openbusiness.

Here we are 12 months down the line and I thought I’d give a little report and comment on what’s going on in the world of P2P/social/web2.0/dis-intermediated finance with a focus on those companies that made presentations. (Little disclaimer: I am a Zopa lender and the links to Zopa are referral links).

Zopa

The concept

Zopa is a social lending platform that matches borrowers with lenders. Lenders deposit their cash, set their interest rates depending on risk category (A*, A, B, C and Y (Young)) and their exposure level (the maximum amount they are willing to lend to one borrower). Borrowers apply and are assigned a risk category. The “matching engine” then does its magic to generate a loan rate. If the borrower accepts, Zopa carries out credit checks and, if successful, the administration of loan repayments. In return they take a percentage fee from lenders on lent out and a flat rate fee from borrowers.

The status in January 2009

£31m in over 7000 loans had been distributed in the UK with 0.2% bad debt since launching in March 2005. Lending fee set at 1% per annum for new borrowers (0.5% for some early members and 0% for those even earlier), borrowing fee at £94.25. They also had operations in Italy since January 2008 and had disbursed €4.3m. The US arm had been halted in October 2008 after only 10 months due to difficult consumer credit conditions. Planned to get involved in Japan.

What’s changed?

Zopa UK has now distributed £60m+ in over 12000 loans with bad debt in the region of 0.7%. The lending fee remains unchanged but borrowers are now charged £118.50. The Italian operation had disbursed a total of €7m before they were suspended in July 2009 by order of banking regulators. They are yet to reopen. Zopa has not re-entered the US market, nor launched in Japan.

The UK team must be pleased with the growth they have experienced with more lent out in 2009 than the rest of the company’s life. Zopa Italy was also showing good growth until the regulatory problems struck. Perusing the the Zopa Forum you do see lenders concerned with rising bad debt rates and the tax treatment of bad debt. Regardless, Zopa is a success story in the P2P finance world.

Kubera Money

The concept

Kubera Money planned an online Rotational Savings and Credit Association (ROSCA). ROSCAs are found in the “real world” all over the world and are an early example of microfinance. In short, a group of n people meet on n occasions. At each meeting, every member contributes an equal amount of money and one member takes the entire sum but only once per cycle of the ROSCA.

The status in January 2009

Claimed to be registering with the FSA and launching soon. They were holding their cards close to their chest regarding the finer details of their model.

What’s changed?

I’ve seen no activity; their blog hasn’t been update since December 2008 and I’ve found no discussion about them elsewhere.

I’m sad about this as I was interested in how popular a service that facilitates formalisation of funding from friends and family would be in the UK especially as Virgin Money has attracted large volumes in the US. Perhaps this venture will be rekindled. However, I do wonder how large the demand would be. Do people want to be involved in a system where saving and borrowing are tied? Would someone looking for a car loan, the most common stated purpose on Zopa, consider using a ROSCA? I think the potential time delay between entering the ROSCA and getting access to the funds could put off a lot of people. I’d especially like to hear any comments you have on this.

Midpoint & Transfer

The concept

To cut out currency exchange middlemen by matching complementary exchanges e.g. Customer A in the UK wants to pay Supplier B in US Dollars. Customer C in the USA wants to pay Supplier D in Pounds Sterling. Via trust accounts, Customer C can pay Supplier B and Customer A can pay Supplier D and no currency exchange is required. In return for organising this Midpoint & Transfer asks for a flat rate fee.

The status in January 2009

Planned on offering the service for a fee of £30 which would give a saving of £100+ on a £10,000 transaction compared to brokers and banks. They were looking for funding to enable the company to match transfers that were left unmatched by other members. PeerFX was already operating, allowing CAD and USD exchange.

What’s changed?

The web presence has disappeared! Another company with the same concept, PeepEX has sprung up but has yet to launch. Todd Veri of Midpoint & Transfer met these guys at MiniBar in August. Perhaps something of a collaboration is on the cards, pure speculation of course. Over in North America, PeerFX is still operational.

The concept seems very sound and if an individual or company £100+can save per transaction I would expect the service to become popular. The major problem is the launch stage where transactions have to be matched out by the service provider. If new members are slow in coming and complementing transactions are thin on the ground, transaction costs could quickly burn into the reserves.

Other news from the sector

Growth is seen at many operations:

• At Lending Club over $300,000 was being disbursed every working day in December 2009, more than double the January 2009 volume.They suffered with regulatory issues in 2008 but these have eased with the primary market open in just over half of US states and the secondary market, where Notes corresponding to loans are traded, is available in all but seven states.

• Smava in Germany disbursed €1.5m+ per month at the end of 2009 compared with around €700,000 at the start of the year (thanks to Wiseclerk.com for these stats). They also expanded into Poland at the start of January 2009 and had facilitated loans of over 30 million Zloty since formation until the end of November 2009 which I make to be £6.5m+.

• Auxmoney, also in Germany, sent out €500,000+ per month at close of 2009 compared to less than €50,000 at the beginning of the year (thanks again to Wiseclerk.com for the numbers).

Decline and apparent closing down is observed elsewhere:

• Virgin Money displayed somewhat of a decline after disbursing approximately $60m in 2009 (based on Wiseclerk.com’s January 2009 datapoint and the Q3 2009 figure from Virgin themselves) compared to $140m in 2008 (based on the same Wiseclerk point and the December 2007 numbers from Virgin). This is probably due to the activity noted over at P2Plendingnews.

Regulatory problems continued to affect players in the world:

• Prosper reopened in late April 2009 after a cease and desist order from November 2008 but was only open to those resident in California. The SEC promptly shut them down again in early May but by mid July the marketplace was up and running again and available in just over half of US states. Around $2m per month was being disbursed in late 2009, compared to $6m per month in the three months before the suspension and a peak of $9m+ in May 2008.

• Loanio has so far failed to reopen after voluntarily suspending operations in November 2008 and registering with the SEC in July 2009.

• As mentioned early, Zopa‘s license to operate as a financial intermediary in Italy was revoked in July 2009 and remains closed to new members.

• Austrian company Bankless Life was ordered to stop making loans in late December 2009.

• IOU Central Canada remains closed since regulators stepped in just weeks after the launch in February 2008. IOU Central USA is yet to get running after filing for registration in May 2009.

• Boober Italy remains closed to new members since Banca d’Italia involvement in late July 2009.

Some players disappeared:

• Boober Netherlands went under in March 2009 after facilitating €1.65 million in loans.

• Perturity Direct was liquidated in August 2009 after only opening in early January 2009.

While others opened:

• isePankur in Estonia
• Aqush in Japan
• CommunityLend in Canada

I will be watching with interest during 2010 to see the winners, losers and new entrants. I will also be keeping a eye on how regulators in different countries deal with the sector.

Up-to-the-minute P2P finance news can be found at P2P-Banking.com, which I highly recommend.

Comments, criticisms, corrections, questions – I welcome them all. Next time I’ll be back to writing about cool science. Stay tuned.

Update:

Between drafting and posting this there’s been a bit of a kerfuffle over the state of Prosper. Mark Gimein published a less than complimentary article regarding bad debt levels. He flags up that over 36% of loans made before November 2007 have ended in default and how from a $136m subset of loans, admittedly classed as high risk, $38m has been written off.

Prosper responded stating that high yields (16%) make up for the bad debt. The problem is that they didn’t. Lenders made a loss of 4% on loans made in or before 2006. On high rate loans (those over 18%) lenders have lost 10% per annum. Prosper goes on to state this is fine because of the recession and makes a dubious comparison to the S&P 500 which lost 6% per annum over the last three years. As rebuttals go, this is not a strong one. To be fair to Prosper, they do describe how their rating methodology has changed to provide a better indication of risk and bravely predict returns of 10% for loans made since these changes. I will be following this with interest.

New(ish) Paper

Here’s a fresh paper that’s got my name on it. Nice collaborative effort with Emi doing the vast, vast majority of the work and Mark being the guiding light.

It’s a warming experience seeing a manuscript come out of the research we do. Performing analysis and referencing wet lab results that corroborate our results are the truly interesting points of molecular dynamics research. Getting the figures looking fit for publication is not so fun, but I’m lucky that Emi dealt with all that.

As the old adage goes, “the proof of the publication is in the citation” and I hope I can look forward to a few of these.

If I want another paper, but with my name in pole position, I’d better get back to work!

No Cell is an Island – What I Do All Day (Part I)

My current area of research/training involves the use of molecular dynamics to investigate membrane proteins. What are membrane proteins, why are they important and why use molecular dynamics? These are questions I hope to answer in my What I Do All Day (WIDAD) series.

Today we’ll start with membrane proteins!

All cells have plasma membranes which are great for separating the interior from the big bad world outside, it’s the bag that holds everything in and keep things out. Some cells also have specialised subunits inside themselves called organelles which are membrane bound. Biological membranes are mainly comprised of lipids with hydrophobic (water hating) chains and a hydrophilic (water loving) head groups. These arrange themselves so the water hating bits are hidden away from water and the water loving bits are bathing in the stuff. The resulting structure is a bilayer as shown below.

Thanks to Jerome Walker for the image

This lipid bilayer is impermeable to all but small and non-charged molecules such as water, carbon dioxide, oxygen, ethanol and urea.

But no cell (or organelle) is an island; they need stuff (carbohydrates, amino acids, nucleotides etc. etc.) to carry out processes (respiration, protein synthesis, replication etc. etc.) and information to react to changing conditions on an environmental, organismal and cellular level such as a change in level of nutrients)

How does stuff and information get through? In the majority of cases, it’s down to membrane proteins. Let’s tackle stuff first. Membrane proteins known as channels, pumps and transporters are the key players and behave as follows:

Channels

These are selective pores in the membrane that allow only a certain chemical or subset of chemicals to move through by diffusion. Aquaporins and potassium channels come to mind as prime examples Peter Agre and Rod MacKinnon won the 2003 Nobel Prize in Chemistry for research into them. Channels are often opened and closed in response to mechanical, electrical or chemical signals.

Pumps

This group actively pumps the desired chemical through the membrane using a chemical called ATP as “fuel”. The ABC (ATP binding cassette) transporters are a major family that import a wide variety of chemicals including maltose and molybdenum in E. coli. They are also responsible for the export of chemicals from cells and are believed to confer resistance to chemotherapeutic agents in cancerous cells.

Transporters

Here the movement of a chemical up its concentration gradient is powered by movement of another, co-tranport molecule (or ion) down its concentration gradient. This co-transport molecule can be moving across the membrane in the same direction as the transport molecular (symport) or in the opposite direction (antiport) as shown below. An example of symport is glucose uptake in the small intestine with sodium ions as co-transport. Antiport is responsible maintaining a high calcium ion concentration in the sarcoplasmic reticulum, an organelle found in muscle cells, priming them for contraction. Sodium ions are the co-transport species.

Modified from original by Zoph

So there you have it; passive diffusion through the membrane would be sufficient if cells just needed to move water, oxygen, carbon dioxide, urea and ethanol in and out but they need far more and proteins facilitate import and export of this stuff.

Next in the WIDAD series: getting information into the cell.

Want to know what a protein is? Don’t know your DNA from your RNA? Coming soon: Biomolecules Demystified.