BRCA2 Cycle Path

I love solving mysteries and problems, which is how I would describe what I do for a living. Technically speaking, I am a biochemist – a structural biologist. I like looking at the 3-dimensional structure of proteins and understanding how other things (other proteins, DNA, small molecules, etc) fit into those proteins. And while I have some interest in understanding the biological processes of cancer, I am not a cancer researcher. However, I have been spending a lot of my spare time trying to understanding more about BRCA2 (pronounced as “bracka two” and stands for Breast Cancer Type 2 susceptibility protein). For most genes and proteins, the gene is in italics while the protein remains in normal font.

BRCA2 was discovered in 1995 by Professor Michael Stratton and Dr. Richard Wooster in cooperation with the Wellcome Trust Sanger Institute. This institute is a charitably funded genomic research center and is located about 9 miles south of Cambridge in a town called Hinxton. The Sanger Institute is a leader in the Human Genome Project, which is an international scientific research project intended to map and identify all of the genes of human genome, both physically and functionally. (Sidenote: a genome is the genetic instructions of how an organism is put together and functions.) From the beginning of the even the idea of the project, there have been strong supporters and strong detractors of this project.

Recently, El’s family has undergone some extensive genetic testing to unveil that some of his family members have a mutation in the BRCA2 gene. His family has a history of breast cancer, specifically related to this gene. Some mutations (but not others) in BRCA2 lead to an abnormal function in the BRCA2 protein. To date, researchers have identified over 450 different mutations in the BRCA2 gene. Some mutations (but not all) of BRCA2 correlated with an increased chance of breast, ovarian, prostate, and pancreatic cancer(s). The mutation that several people in El’s family have causes the BRCA2 protein to be truncated; thereby, causing a reduction in the function of the protein. Why does this all matter? Well, the protein created by the BRCA2 gene is involved in repairing damaged DNA. It binds to and regulates another protein (RAD51) in order to fix breaks found in your DNA. Breaks in DNA happen, which is why your body has a system to repair them. It is only when there are (certain) mutations BRCA2 that result in the cells dividing in an uncontrollable way (this is pretty much the textbook definition of cancer).

Being so far away from El’s family, there really isn’t too much we can do as each member of his family has genetic testing done and then determining what to do with those results. I am so amazed at how his family is coping with the results, especially one person in particular. The level of determination and sustained hope she has is so inspiring, and I admire her for how she (and the rest of his family) are tackling the situation. Therefore, when I discovered there was a BRCA2 cycle path, I knew I had to ride it, no matter the distance (for the record, it is approximately 2 miles long). This cycle path is part of the National Cycle Network in England and extends from the Addenbrooke’s Hospital site (where I work) with a nearby community called Great Shelford. At its unveiling in 2005, it was the 10,000th mile of the National Cycle Network. To represent the 10,257 base pairs of the BRCA2 gene, a series of thermoplastic stripes were heat welded in four different colors and represent the nucleotide sequence of BRCA2. The color scheme is the following: green is adenine (A), red is thymine (T), blue is cytosine (C), and yellow is guanine (G). At each end of the cycle path is a metal structure of the DNA double helix.

Double helix of DNA

DNA double helix

BRCA2 cycle path

BRCA2 cycle path

10,000 mile, 10,257 stripes

10,000 miles, 10,257 stripes

Our Year Five Began in Paris

Before we moved across the pond, my friend Mary Anne suggested that we should celebrate our fifth wedding anniversary by being in Paris and in the Eiffel Tower. I become fixated on doing this because I thought it would be a very romantic way to celebrate. I was envisioning eating chocolate and drinking champagne at the top by ourselves – yes, in my mind, all of the other tourists would just not be in the tower with us. Maybe El rented the tower for the day to celebrate. Who knows? It could happen, right? Let’s just say that I can be a little delusional at times!

This was our second holiday (the first being a tour of East Anglia in July), but our first one to “the continent.” By which, I mean continental Europe, which excludes all of the islands that are associated with Europe. In other words, Brits refer to Europe as this other place that excludes them. And while I don’t disagree that British people and their customs are wildly different from other Europeans, I find it strange that the Brits commonly exclude themselves from the rest of Europe. Examples include: UK is the only place in Europe that drives on the left side of the road, thereby needing to have right-side driver seats; the UK is the only country (edit: one of ten countries, soon to be nine) in the EU that does not use the Euro as currency. The other countries that do not use the Euro are Bulgaria, Croatia, Czech Republic, Denmark, Hungary, Poland, Romania, Sweden, and Lithuania. However, Lithuania is set to start using the Euro in January 2015. (Thanks Nesrin for the information about the EU countries that haven’t adopted the Euro!)

I digress. Back to France! We had an ambitious list of things that we wanted to see and do in Paris, but we’d only be around for two and half days. Therefore, we opted for subway tickets that would let us freely roam within Parisian Zones 1-3 (the main portion of the city) and tried to group together things based on their locations. We still have a few things that we would have liked to do, but we plan to be in France again in the next few years. We envision the possibility of stopping in Paris for another day or two on the way to somewhere else.

Here’s a photo-essay with a sprinkle of information and/or history on what we did for the ~70 hours that we were in Paris:

Musée du Louvre
Famous for the pyramid shaped sculpture and for being the site of Leonardo da Vinci’s Mona Lisa painting, the Louvre is a fantastic museum full of sculptures, paintings, and textiles. The museum contains thousands of works of art divided into several departments: Near Eastern Antiquities, Egyptian Antiquities, Greek, Etruscan and Roman Antiquities, Islamic Art, Sculptures, Decorative Arts, Paintings, Prints, and Drawings. The span of the museum is extensive because it has been so much more than just a museum. In 1190, The Louvre was built as a fortress to protect Parisians from possible invasions from the north (I would have feared Viking attacks too). In the 16th century, the Louvre was reconstructed as a royal palace. And finally, in 1793 the Louvre became a fine art museum.

Louvre 5

We roamed through the never-ending hallways and stairwells for hours with Nintendo 3DS consults as our tour guides – they are totally worth the 5 Euro. There is at least one stairwell that goes under the museum, which is pretty interesting to see the foundation of the original building! I was really struck by various artists sitting in front of fantastic pieces of work with their own paintbrushes and canvas, trying to recreate the original. I also found one of my new favorite pieces of artwork by exploring the Louvre.

Louvre 2

Fun fact for others (and maybe ourselves): on the first Sunday of the month during off-peak travel season (from October until March), all visitors can access the permanent collections of the museum for free. It is not free between April and September. Also, the museum is closed on Tuesdays year-round.

Arc de Triomphe de l’Étoile
This arch monument is not to be confused with the one just outside of the Louvre Museum – that one is the Arc de Triomphe du Carrousel and is about half the size of the one in Place de l’Étoile. This monumental and triumphal arch was inspired by the Roman Arch of Titus, which was built in 92 BCE. The construction of the Arc de Triomphe de l’Étoile started in 1806 (completed 30 years later) and is one of the largest triumphal arches in the world, standing at 164 ft (40 meters) in height, 148 ft (45 m) in width, and 72 ft (22 m) deep. To put that into perspective, after the hostilities of World War I ended, Charles Godefoy (aviator in the French Air Force) flew his Nieuport fighter biplane through (THROUGH!) the arc. This event has been captured on film and in photos.
Currently, there are two larger triumphal arches: the Monumento a la Revolución in México, D.F. (Mexico City) standing at 220 ft (67 m) tall, which was built in 1938, and the Arch of Triumph in Pyongyang, North Korea standing at 197 ft (60 m) tall, which was built in 1982. The Arc de Triomphe de l’Étoile honors those who fought and died for France in the French Revolutionary War and in the Napoleonic War. The names of all the French victories and generals on carved into the surface of the arch. Beneath the vault is the Tomb of the Unknown Solider from World War I. Many days, there is also a colossal French flag flying under the archway as well.

Arc 1

As we approached the Arc de Triomphe, we couldn’t figure out how exactly to get there. The Métro (Parisian subway) stop is Charles de Gaulle – Étoile station, which plops you out close, but on one of the adjacent streets coming off of the roundabout. Did I mention this arch happens to be in the center of a roundabout? And this roundabout is at least a few lanes deep and is the intersection of 12 roads! Because of the traffic, it is highly recommended to use the pedestrian underpass (located at Champs Élysées and the Avenue de la Grande Armée). In fact, I don’t think you could make it across the roundabout road without getting injured.

After marveling at the outside design of the Arc de Triomphe, we decided to go to the top. The spiral staircase to the top consists is just shy of 300 steps. At the top you arrive at a small gift shop and exhibition to learn more about the monument’s history. There are about another 50 steps to reach the rooftop of the monument, where you have a panoramic view of Paris. One can see the Place de la Concorde, the Jardin des Tuileries, the Louvre Museum, the Basilica, and the Eiffel Tower. I personally believe that this is one of the most amazing views of Paris.

Arc PANO top-001

The 18th Arrondissement
The 18th arrondissement (district) is on the north side of Paris and is known for a many things. One of which is the Sacré-Cœur Basilica (Basilica of the Sacred Heart of Paris). After researching a little bit about what exactly a basilica is, the word has three separate meanings, which is why I’m probably still a little confused. A basilica can be used it to describe a building, usually Roman and an open public court building. Another way it is used is to architecturally describe Christian churches that have a central nave and aisles. The third way specifically describes churches that have Papal rights to perform specific ceremonies. One thing is for sure, the Sacré-Cœur Basilica is a Christian church with a central nave and aisles.

Basillica 4

Sacré-Cœur Basilica is a Roman Catholic church at the summit of Montmartre, a 427 ft (130 m) tall hill, which happens to be the tallest point in Paris. Also on this hill is another church; the Saint Pierre de Montmartre, the older of the two churches on the Montmartre hill, which claims to be the location where the Jesuit order of priests was founded.
Montmartre also describes the surrounding neighborhood, which is part of the 18th arrondissement. This area is also known for Moulin Rouge (we only stopped outside of to take a photo or three) and the Place du Tertre, which is a square where some artists make portraits for tourists while other artists are painting landscape scenes of Paris – to sell to tourists. This area is apparently also known for being the night club district and has been the site where many artists have lived in Paris. The museum of Salvador Dalí‘s drawings and sculptures is also within this district. I think our favorite part of this neighborhood was the views of the city and watching a mime entertain the crowd outside of the basilica.

Basillica 1Moulin Rouge

Cathédrale Notre Dame de Paris
Notre-Dame de Paris is a historic Catholic cathedral in the 4th arrondissement of Paris on the eastern part of the Île de la Cité, one of two natural islands* in the Seine River within Paris. The architecture of the cathedral is stunning along with the stained glass and sculptures within the cathedral. It is also the location of the Archdiocese of Paris and contains the treasury notable for its reliquary; it is the home of the Crown of Thorns, part of the True Cross, and one of the Holy Nails. There are ten bells in the cathedral, which to my amusement are all named. The largest (and oldest), Emmanuel, is original to 1681 and weighs over 13 tons. That’s a BIG bell! It is mostly used to mark the hours of the day. The other nine bells (names are: Marie, Gabriel, Anne Geneviéve, Denis, Marcel, Étienne, Benoît-Joseph, Maurice, and Jean-Marie) were replaced in 2013 and are rung for various festivals or ceremonies. My friend Dan also recently pointed out that just outside of the main entry, there is a small octagonal brass plate set in the ground which marks “Paris Point Zero” – the  exact spot from which all distance from Paris are measured. We completely walked by it without noticing it.

Notre Dame 5

*As a side note, there is an artificial island on the Seine River. One of them is Île aux Cygnes, which is where there is a replica of Statue of Liberty. This statue is one quarter of the size of the one located in the USA.

The Eiffel Tower

On to the grand prize of this adventure. The Eiffel Tower happens to have many replicas – one of which we visited in June of this year in Las Vegas, Nevada. But we wanted to see the real thing. Remember? El was to have rented out the tower for a day to celebrate our anniversary without other tourists. The iconic iron lattice tower is located near the Seine River and on the Champ de Mars. It was named after the engineer (Gustave Eiffel) and was constructed to be used as the entrance to the 1889 World’s Fair. Gustave Eiffel has an impressive list of things he has designed; another popular attraction he designed is the Statue of Liberty.

Eiffel Tower 1

We first admired the tower from the Champ de Mars, the adjacent park. The park has a lot of history that goes with it. The world’s first hydrogen-filled balloon was launched from there in 1783. In 1790, the first “Federation Day” (Bastille Day) celebration was held there. A year later, the massacre on the Champ de Mars also took place. And he first mayor of Paris (Jean Sylvain Bailly) was guillotined there in 1793, becoming a victim of his own revolution. Only the French.

We had a little picnic with some wine and soaked up the sun on the green. Our nearest neighbors in the park were also soaking up the sun in swimsuits, which we found to be pretty awesome since they all looked to be around our grandparents’ ages. We then took a few pictures “with the tower” before climbing all of the stairs. All 704 of them to the second level. There are three levels for visitors – the first two levels have restaurants and gift shops on them. There was also a movie showing the construction of the tower and views of the tower throughout its history; the film ended with panoramic views of fireworks at the tower. One the day that we went, the third and final level was inaccessible by stairs, so we stood in line to take an elevator to the top deck observatory. The top level is 906 ft (276 m) from the ground, making it the highest accessible public platform in the EU.

Eiffel Tower Picnic 5                 Eiffel Tower Picnic 4

My thoughts of the City of Lights

From what we did see and experience of the city: the food and culture are nothing like we’ve experienced. Every wine we tasted was fantastic, but I couldn’t tell you what type of wine. The city views from the Eiffel Tower, Arc de Triomphe, and Basilica are all very different, but my favorite was from the top of the arc. With an app, the subway system was easy to navigate. The local people (away from the city attractions) were quite friendly – we used an app that had common French phrases, which helped with communicating to non-English speakers (they appeared to be thankful that we were trying to speak French). The lesson we learned for our next adventure: bring a second pair of shoes! The pedometer on my phone estimated that we walked about 100,000 steps the four days that we were in London and France. I say that this was by far our healthiest vacation!

Remember, Remember

Today is the 5th of November. And to Americans, this is just another day. In England, today is a day to celebrate! And to light bonfires and fireworks! And for remembrance.

Today’s post is about history of today and the history leading up to today. First, let’s first go through some historical perspective on monarchies and the messes they created along the way.

The family tree of the House of Tudor members. Monarchs of England shown in red, monarchs of Scotland shown in blue. Source: wikipedia.

The family tree of the House of Tudor members. Monarchs of England in red, monarchs of Scotland in blue. Source: wikipedia.

Henry VIII is known for a couple of things:
1) having six wives
2) creating the Church of England (the separation from the Roman Catholic Church is called the Reformation) – he declared himself the Supreme Head of the Church in 1534. This is where the title “Your Majesty” originates.
3) having an awful temperament and beheading anyone that upset him – this list of people include wife #2 (Anne Boleyn) and wife #5 (Catherine Howard). Anyone who publicly disagreed with the Church of England was executed as well.
4) he was King of both England and Ireland
5) he had three children, two daughters and a son – interestingly, all of them became the King or the Queen of England

Henry VIII and his first wife (Catherine of Aragon, who was the widow of his older brother Arthur) had one child whose name was Mary (later becoming Queen Mary I, but popularly called Bloody Mary). After being married to Catherine of Aragon for 18 years, Henry VIII decided that it was bad luck to have married his brother’s widow; this luck was clearly the reason for not having more children, particularly a son as an heir to the throne. Therefore, he divorced and annulled his marriage to Catherine of Aragon in order to marry wife #2 – Anne Boleyn. Anne would later gave birth to Elizabeth (later becoming Queen Elizabeth I). He beheaded Anne and married wife #3 – Jane Seymour; she died shortly after giving birth to Henry VIII’s only male heir, Edward (later becoming King Edward I). Wife #4 was Anne of Cleves. Henry VIII and Anne Cleves were divorced after only being married for six months. Wife #5 was Catherine Howard – she was executed, and wife #6 was Catherine Parr. Catherine Parr outlived the King and later remarried again (for the fourth time). However, Catherine Parr convinced Henry VIII to pass the Third Succession Act in 1543, which would restore the line of succession to the throne to both of his daughters.

After King Henry VIII died, his only son, Edward, became the next monarch of England and Ireland under the title King Edward VI. Edward VI was a Protestant king at the ripe age of 9. Succession became a big issue in England because he was really sick. Many wanted to keep Mary (King Henry’s first child) off of the throne because she was Catholic; others claimed that both Mary and Elizabeth were illegitimate for the throne, even though the Third Succession Act of 1543 named Mary as the next heir.
Four days after Edward VI died, Lady Jane Grey was proclaimed Queen of England (and Ireland). She was Edward’s cousin – King Henry VIII’s niece and the next heir to the throne (if you thought Mary and Elizabeth were illegitimate). Lady Jane Grey was proclaimed Queen by the Duke of Northumberland (John Dudley). John Dudley was the head of King Edward I’s government and happened to be Lady Jane Grey’s father-in-law. Coincidence? I think not. Now, if I was Mary or Elizabeth (Henry VIII’s daughters), I would have been angered by this. Mary made a counterclaim saying that she was the rightful heir of the throne, which gained a lot of support. Lady Jane Grey was executed after being Britain’s first Queen Regent (her reign of only 9 days is the shortest reign in British history).

Queen Mary I was crowned in July of 1553. Just as a reminder, she was Catholic and was the first child of King Henry VIII (and wife #1 – Catherine of Aragon). However, after her parent’s marriage was annulled, she was stripped of her title, declared illegitimate, and expelled from the court, which mostly likely made her very resentful towards Protestants. However, because of her mistreatment, Mary I had huge support as Queen initially, but it was short-lived. Her marriage to the future King of Spain (Phillip II) was very unpopular to the English. And she became a tyrant, burning hundreds of religious dissenters (non-Catholics) at the stake, which earned her the popular nickname of Bloody Mary. Mary and Phillip were childless; therefore when Mary passed away, the crown succeed to her Protestant half-sister Elizabeth.

Elizabeth was the second child of Henry VIII (and wife #2 – Anne Boleyn). She reigned for forty years and restored a lot of peace to the country. The Protestant Church of England had been created by her father and continued by her half-brother Edward I. However, her half-sister Bloody Mary attempted to restore Catholism to England and did it in a not-so-nice way. Queen Elizabeth I rejected the extremes of both Protestant and Catholic religions; she favored a more moderate Protestant religion with some Catholic traditions. For whatever reason, she never married and declared herself married to England. She is well known for this and for the resurgence of literacy and exploration under her reign as Queen.

Meanwhile, the following was happening in Scotland
(warning: the following information is very heavy because of all of the people named Mary or James):

1. King Henry VIII’s sister (Margaret Tudor) married King James IV of Scotland (reigned 1488-1513); they had a son (King James V of Scotland, reigned 1513-1542).
King James V married Mary of Guise had a daughter named Mary; she became Queen of Scotland (reigned 1542-1567 better known as Mary Queen of Scots). And because it becomes important later, Mary Queen of Scots was Catholic.

2. After King James IV of Scotland passed away, Margaret Tudor married Archibald Douglas. They had a daughter named Mary. Just joking! – they named her Margaret [Douglas].
Margaret Douglas married Matthew Stuart and they had a son named Henry Stuart, whose title was [English Catholic] Lord Darnley.
Henry Stuart (Lord Darnley) should not be confused with the third husband of his grandmother (Margaret Tudor) – his name was Henry Stewart.

3. Mary (as in, Mary Queen of Scots) married her cousin Henry Stuart (Lord Darnley) and they had a son, James (he would later become King. Twice.) Due to Henry Stuart (Lord Darnley)’s mysterious death and Mary Queen of Scots subsequent marriage to James Hepburn (Protestant Earl of Bothwell), a civil war broke out in Scotland. Mary Queen of Scots’s side lost this war. She was imprisoned and forced to abdicate the throne to her son (James) who was named King James VI of Scotland at the age of 1 and was brought up as a member of the Protestant Church of Scotland.

4. After breaking free from Scottish imprisonment, Mary Queen of Scots eventually fled to England to seek the mercy of Queen Elizabeth after that whole mess. Mary Queen of Scots was then imprisoned in England for 19 years under Queen Elizabeth’s rule – until Elizabeth had Mary Queen of Scots beheaded.

5. James VI of Scotland (son of Mary Queen of Scots and Henry Stuart (Lord Darnely)) and was the great-grandson of King Henry VII of England. He supported Queen Elizabeth I against (Catholic) France and Spain. Technically, Queen Elizabeth I of England (and Ireland) was King James VI of Scotland’s godmother. Because of all of this, it does seem fitting that when Queen Elizabeth I passed away (childless), she named James VI of Scotland the King of England/Ireland. Therefore, he is known as James VI of Scotland and King James I of England and Ireland – or for clarification James I/VI. This is where England, Ireland, and Scotland come together for the first time under one crown (the Union of Crowns).

Now all of that history leads to the history of today – the 5th of November!
The Gunpowder Plot of 1605 was devised to restore civic rights to Roman Catholics in England. A group of Catholic extremists planned to wipe out King James I/VI and his Protestant Parliament, then put one of his children on the throne as a puppet supporting Catholic causes. The Gunpowder Plot’s explosive expert was named Guy Fawkes. There were 36 barrels of gunpowder were planted under the House of Parliament. Because a Catholic Parliament member was advised to not attend Parliament on the night of November 4, suspicion caused guards to investigate. They found the explosives being guarded by Fawkes, who was arrested and tortured until he named the other conspirators. They were sentenced to be hung, drawn, and quartered. (Ew.)

In the aftermath of the failed conspiracy to assassinate the King James I/VI, his council allowed the public to celebrate his King’s survival by lighting bonfires. The following year, the Observance of the 5th November Act was passed, which suggested that the king’s apparent deliverance by divine intervention deserved official and public recognition. For a long time, there was a long history of anti-Catholic sentiment, which was expressed and prominently displayed on November 5 by burning effigies of Guy Fawkes in bonfires. The modern November 5 celebrations are now mostly ran by volunteers and paid for by local charities or with paid admission and controlled access to spectators.

Tonight, we walked to a nearby park (Midsummer Common) where there was a fireworks show and a large bonfire along with carnival rides. There were volunteers maintaining the bonfire and other volunteers holding buckets for donations to cover the costs of the celebrations. For me on this November 5, I remember that lighting a giant bonfire and setting off fireworks have a deep footed history and are tradition in the UK. However, more importantly, I remember that hate, crime, and inequality are still present in the world, but unnecessarily so. We all have a responsibility to be a part of a movement to change the world that we live in today to be more peaceful, respectful, and tolerant one.